bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional models of care for systemic therapy: Standards for organization and delivery
Authors: Vandenberg T. , Smith A. , McLennan C. , Wilcock L. , Nayler J. , Coakley N. , DeGrasse C. , Green E. , Sawka C. , Trudeau M. E.
Published: March 2020

17057

Background: Rapidly expanding indications for cancer systemic therapy combined with human resource and facility constraints require innovative approaches to deliver safe, patient-centred, and evidence-based care across Ontario, a province covering 1 million sq km, organized into 14 regions, each with about 1 million inhabitants. A systemic therapy project team recommended the best way to organize the delivery of ambulatory systemic therapy in Ontario. Methods: A core multidisciplinary panel reviewed the evidence and developed standards. The panel used evidence-based analysis of relevant publications, an environmental scan of other existing recommendations and expert opinion based on experience and consensus to formulate a standards document to guide treatment delivery. This was reviewed and amended by the full project team. The document was circulated to oncologists, family practitioners, internists, pharmacists, nurses and administrators who work in or have responsibility for systemic therapy in the regions for practitioner feedback. Results: A Regional Systemic Therapy Program (STP) Model was developed in which Integrated Cancer programs (ICPs) provide comprehensive cancer services, leadership of quality and overall organisation/coordination for the region. STPs include ICPs directly linked to satellite centres and also affiliated to centres with their own systemic therapy programs to provide appropriate systemic therapy services for all regions under a common set of standards. Five levels of care are recommended, with complexity and availability of services differentiating the levels. For each level, standards were established for; 1-Providers and their roles, 2-Education for providers, 3-Service type and complexity, 4-Service volumes, 5- Quality assurance and safety, 6-Facility requirements, 7-Administrative and organizational responsibilities. The intent is to provide the same standard of care in the most appropriate setting within the appropriate time frame. STPs will implement, monitor and evaluate quality indicators. Conclusions: A detailed review of the document including results of practitioner feedback as well as survey results from the 14 STPs to determine whether standards are being currently met will be presented.

No significant financial relationships to disclose.
Hematologic outcomes and drug cost considerations of erythropoiesis stimulating agents (ESTs) in cancer patients (pts) with fixed dosing regimens: Results from practice patterns in a prospective observational study
Authors: Larholt K. , Chen E. , Peake C. , Bookhart B. , Piech C. Tak , McKenzie R.
Published: March 2020

17063

Background: The erythropoietic agents available today have FDA-approval for weight-based as well as fixed dosing in cancer pts with chemotherapy-induced anemia [epoetin alfa (EPO) 40,000 Units QW, darbepoetin alfa (DARB) 500 mcg Q3W]. To understand hematologic outcomes and EST cost considerations based on actual patterns of use, not protocol-driven use, data were analyzed from the Dosing and Outcomes Study of Erythropoiesis-Stimulating Therapies (D.O.S.E.) Registry, an ongoing registry of real-world practice. Methods: Data from 18 U.S. practice settings from 1/06–12/06 were assessed. Chemotherapy-treated adult cancer pts initiated at either EPO 40,000 Units or DARB 500 mcg were evaluated. Outcomes assessed included mean treatment duration, hematologic outcomes, mean administered dose, mean cumulative administered dose, and total EST cost (based on 9/2006 wholesale acquisition cost). Results: 168 pts (145 EPO, 23 DARB) were eligible. Patient groups were similar with regard to baseline age, gender distribution, tumor type, Karnofsky score and Hb. Treatment duration was similar for both agents, approximately 7 weeks. The proportion of pts transfused from Week 5 to end of study and number of units/ pt was not significantly different between groups (% transfused: EPO 10%, DARB 13%; Units/pt: EPO 0.2, DARB 0.3). Mean administered dose was 42,879 Units in the EPO group and 497 mcg in the DARB group. Mean cumulative administered dose for the treatment episode was 305,241 Units for EPO and 1,665 mcg for DARB, corresponding to an EST cost of $3,715 for EPO and $7,404 for DARB (p <.0001). Conclusions: Real-world practice pattern data from this observational study found similar treatment duration and transfusion patterns in the EPO-treated group versus the DARB-treated group in pts initiated with FDA-approved fixed dosing regimens. Cumulative EST cost was $3689 lower in the EPO group, a 50% reduction versus the DARB group.

No significant financial relationships to disclose.
Comparison of the demographics of patients enrolled (E) versus those not enrolled (NE) on therapeutic clinical trials at a comprehensive cancer center
Authors: Goodin S. , Vamos D. C. , Kane M. P. , Nishioka J. , Lisi S. , Neceskas J. R. , Aisner J. , Rubin E. H. , Todd M. B. , Shih W. J.
Published: March 2020

17065

Background: In the U.S., representation of minorities and the elderly in clinical trials has been low yet few reports have evaluated this potential barrier to enrollment by comparing the demographics of patients E vs NE within an institution. Therefore, we compared these groups to determine if there were significant differences in demographics at our center. Methods: For all E patients, demographic data is collected in a clinical trial database. For evaluated NE patients, data was captured through a ‘non-protocol’ form. A univariate analysis was performed on the demographic data, including gender, age, race, and insurance status, for each year to determine if there were differences in patients E vs NE on a therapeutic clinical trial. Results: From June 2003 through December 2005, there were 912 E patients and data available on 474 NE patients. The results were consistent for each year from 2003 to 2005, and therefore combinable, with no statistical difference in any parameter for E patients versus NE patients during any year with the exception of gender (p=0.05; Chi-square). The distribution of patients E by gender is 52% (474/912) female vs 48% (438/912) male and NE is 69% (325/474) female vs 31% (149/474) male. The mean age of E patients was 55 vs 56 years for NE patients, with 32% vs 33% representing those >65years, respectively. For the E patients, 84% were white, 7.2% black, 4.6% Asian, 4.2% unknown, and 0.4% Hawaiian/Pacific Islander (H/PI). For the NE patients, where race was not consistently available, 65% were white, 9.3% black, 3.2% Asian, 20.5% unknown, and 2.1% H/PI. In both groups, most patients had private insurance (E 60%, NE 54%), followed by Medicare (E 27.5%, NE 29%), Medicaid (E 4%, NE 9%), self pay (E 7.5%, NE 7.4%), and unknown (E 1.3%, NE 0.4%). Conclusions: When comparing E vs NE patients, gender was the only factor that differed significantly. Although this result suggests that males were more likely to be E in a clinical trial, this finding should be interpreted with caution, since this difference might relate to differences in trial availability. While lower enrollment rates for the elderly and minority patients have been identified nationally, enrolling this group of patients does not appear to be a barrier at our center.

No significant financial relationships to disclose.
Knowledge of cancer clinical trials in screened populations
Authors: Walsh J. H. , Sahasrabudhe D.
Published: March 2020

17076

Background/Methods: Previously, we reported results regarding knowledge of cancer clinical trials in men undergoing prostate cancer screening. We administered the same questionnaire to 103 women undergoing screening mammography at a single center. We report results from both studies here. Results: The mammography screening group was racially homogeneous as compared to the prostate cancer screening group. Fewer than 3% of women were nonwhite compared to over 20% of men. Fewer women reported college education, 49% vs. 79%. Half the women were employed compared to a third of the men. On 81% of test questions, participants in the breast cancer screening group chose the correct answer 80% or more of the time. This compared to 71% in the prostate cancer screening group. The mean percent correct answers in the breast group was 91% as compared to 82.4% in the prostate group. Women were significantly more knowledgeable about trial oversight, rationale behind clinical trials, and blinding. Randomization and use of placebo were poorly understood by both groups, with 45% of men and women incorrectly answering a question regarding placebo. Univariate t-tests and multi-way ANOVA analyses suggest that college educated women are significantly more knowledgeable about clinical trials. Race, income, employment status, and marital status did not have a significant effect on women's knowledge. When the breast and prostate data were combined in univariate analysis (see table ), gender, college education and race were found to significantly affect knowledge of clinical trials. These findings maintained significance in multi-way ANOVA analysis. Conclusion: In this hypothesis-generating study, white, female, college educated subjects were more knowledgeable about clinical trials. Importantly, similar knowledge gaps were observed in both studied groups. Targeted interventions to educate patients about the rationale behind clinical trials, randomization, and use of placebo may help increase accrual in clinical trials.

[Table: see text]

No significant financial relationships to disclose.
Validation of 12-item general health questionnaire into Kannada language
Authors: Javaregowda D. C. , Parthasarathy B. , Suresh A. , Lokanath D. , Govind Babu K. , Ullas B. , Anupama G. , Sani K.
Published: March 2020

17077

Background: The cancer load in India is enormous and majority of the cases present in an advanced stage. There is no valid translation of 12-item General Health Questionnaire (GHQ-12) in Kannada, which is a simple but indispensable tool in the comprehensive cancer care (both for metastatic and in adjuvant settings). Therefore we thought of developing and validating the GHQ-12 Questionnaire into Kannada language. Methods: The study was conducted at kidwai memorial institute of Oncology, Bangalore, a tertiary cancer center with an annual attendance of 16,000 new cases. We have chosen educated patients who can speak and write both English and Kannada. We used ’forward-backward’ translation procedure into Kannada. We used scores from 0–3 for the Questionnaire. Total score for both languages was calculated. Internal consistency was assessed by Cronbach's alpha coefficient. Validity was performed using convergent validity. Finally, the factor structure of the questionnaire was extracted by performing principal component analysis using oblique factor solution. Results: A total of 118 patients with various malignancies were entered into the study. The mean age was 36.8 ± 12.1 years. The mean GHQ score was 21.6 ± 9.1 for the English and 22.6 ± 8.1 for Kannada. Reliability analysis showed satisfactory result (Cronbach's alpha coefficient = 0.79). The principal component analysis with oblique rotation solution showed that the GHQ-12 was a measure of psychological morbidity with four -factor structure that jointly accounted for 48 % of the variance. Conclusions: The Kannada version of the GHQ-12 is a reliable and valid instrument with a good structural characteristic. It can be used for measuring psychological well being at our institute for those patients who can read and write only Kannada.

No significant financial relationships to disclose.
Aberrant immunophenotype in acute myeloid leukemia (AML): High frequency and association with dysplasia
Authors: Dogra S. , Mangipudy J. P. , Asatiani E. , Gamez R. , Cohen P. , Kessler C. , Mavromatis B. , Shad A. , Cheson B. D. , Ozdemirli M.
Published: March 2020

17504

Background: Asynchronous expression of immunophenotypic markers on AML myeloblasts has been well described, but the association of aberrant phenotype with morphologic subclasses has not been reported previously. Methods: Multiparameter flow cytometry (MFC) data were analyzed for all patients (pts) diagnosed with AML at our institution from 2000–2006. MFC was done on fresh bone marrow aspirate and/or peripheral blood samples using the following panel of monoclonal antibodies in triple staining: CD2, CD3, CD4, CD5, CD7, CD8, CD10, CD11c, CD13, CD14, CD15, CD16, CD19, CD20, CD22, CD24, CD33, CD56, CD34, CD117, HLA-DR and TdT. Identification of myeloblasts was performed using Side Scatter (SS) characteristics and CD45 expression. Acute lymphoblastic leukemia (ALL) cases or cases with mixed lineage acute leukemia were excluded from the study. Results: We identified 76 pts with AML; median age 57, (range 10 weeks to 89 years), with 32 males and 44 females. The patients had the following French American British classification of AML: M0 (n=1), M1 (n=11), M2 (m=10), M3 (n=5), M4 (n=13), M5 (n=14), M6 (n=1), M7 (n=4) and not otherwise categorized non- M3 AML (n=17). Twenty two pts had AML with multilineage dysplasia (AML-MD) as classified by World Health Organization. Coexpression of TdT on myeloblasts was observed in 4 pts, one of these coexpressed CD5. T-cell lymphoid associated antigens (CD2, CD5 and/or CD7) were coexpressed on myeloblasts from12 pts. B cell lymphoid associated antigens (CD19 and/or CD20) were expressed on myeloblasts from11 pts. Both T and B cell lymphoid associated antigens were present on myeloblasts in 4 pts. Myeloblasts from 13 pts demonstrated the presence of the NK cell marker CD56. A total of 43 patients had AML with immunophenotypic lineage infidelity manifested by coexpression of one or more aberrant antigens on myeloblasts. The distribution of cases with lineage infidelity was higher in 22 pts with AML-MD (n=17, 77%) versus in 54 pts with no dysplasia (n=26, 48%), Chi square =5.4, p=0.02. Conclusions: Abnormal coexpression of lymphoid and NK cell markers was observed in significant number of AML pts and correlated with the presence of multilineage dysplasia. This finding may indicate an earlier stem cell origin of AML-MD.

No significant financial relationships to disclose.
Therapy-related myelodysplastic syndrome (t-MDS) following treatment of acute myeloid leukemia (AML)
Authors: Arana-Yi C. , Block A. W. , Sait S. N. , Ford L. A. , Barcos M. , Baer M. R.
Published: March 2020

17509

Background: t-MDS is well described following treatment of lymphomas, solid tumors and acute promyelocytic leukemia. In contrast, it has been reported only rarely following treatment of AML, possibly because of the smaller percentage of long-term survivors or the difficulty of distinguishing t-MDS from AML relapse. Methods: Roswell Park Cancer Institute (RPCI) patients with a diagnosis of MDS by French-American-British or World Health Organization criteria following a diagnosis of AML were retrospectively reviewed. Results: Five adult patients treated for de novo AML between 1996 and 2005 developed MDS, representing less than 1% of 548 RPCI AML patients during those years. MDS presented as cytopenias and marrow dysplasia, occurred 11 to 101 (median 27) months after diagnosis of de novo AML, and was associated with chromosome 7 abnormalities, including monosomy 7 or del(7q), in all five. All had been treated with cytarabine and topoisomerase II inhibitors and three had received alkylating agents as part of autologous transplant regimens. All had received granulocyte colony-stimulating factor or granulocyte-monocyte colony-stimulating factor in conjunction with chemotherapy and/or autologous transplantation. Fluorescence in situ hybridization with the CEP 7 probe or the dual-color LSI D7S486 (7q31)/CEP 7 probe set did not demonstrate chromosome 7 abnormalities in marrow prior to MDS diagnosis nor in peripheral blood stem cells of patients who had undergone autologous transplantation prior to diagnosis of MDS. MDS has progressed slowly in all patients; it evolved to AML in two following 18 and 24 months. Conclusions: These cases further document t-MDS following AML therapy. Presence of chromosome 7 abnormalities in cases without, as well as with, prior alkylating agent therapy suggests possible association with the anti-metabolite cytarabine.

No significant financial relationships to disclose.
Chronic myeloid leukemia with variant translocations: A cytogenetic profile
Authors: Saini K. V. , Kumari P. , Saini M. L. , Latha P. , Jain A. , KV S. , Batra U. , Attili A. , Lakshmidevi V. , Lakshmaiah K. , Bapsy P.
Published: March 2020

17517

Background: Chronic Myeloid Leukemia (CML) is characterized by the translocation between chromosomes 9 and 22. The resulting Philadelphia chromosome is the cytogenetic hallmark of this disease. Occasionally, other variant translocations may be present. Methods: We performed a retrospective analysis of case records between 1999 and 2006 of patients diagnosed with CML at the Kidwai Memorial Institute of Oncology, a tertiary care cancer centre in South India. The cytogenetic profile of CML patients was determined. Results: The total number of CML patients (proven by bone marrow aspiration) diagnosed at our centre during the study period was 1268. Of these, 79 cases (48 M, 31 F) had variant translocations ( Table 1 ). The mean age at diagnosis was 35.9 yrs (SD 11.4). The involved chromosomes were 22 (91.1%), 9 (69.9%), 1 (13.9%), 19 (11.4%), 12 (8.8%), 7 (7.6%), and 6 (7.6%). Other involved chromosomes were 11, 2, 3 13, 15, 17, 16, 20, 21, and 8 in decreasing order of frequency. Table 1 : Cytogenetic Profile of CML Conclusions: Other than chromosomes 22 and 9, the variant translocations commonly involved chromosomes no 1, 19, 12, 7, and 6. The identification of these variant translocations and their co-relation with the clinical behavior may identify new prognostic markers.

[Table: see text]

No significant financial relationships to disclose.
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.

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Wood-smoke exposure as a survival predictor in non-small cell lung cancer with response to erlotinib: An open label phase II study
Authors: Arrieta Rodriguez O. G. , Tellez E. , Martinez-Barrera L. , Castillo P. , Reyes-Contreras J. , Flores-Estrada D. , Hernandez- Pedro N. , Morales-Espinosa D. , Ceron-Lizarraga T. , De la Garza-Salazar J.
Published: March 2020

18029

Background: Erlotinib, a tyrosine kinase inhibitor, has improved survival and quality of life in patients with non-small cell lung cancer (NSCLC) after fist-line or second-line chemotherapy. Asian origin, adenocarcinoma histology, female gender, lack of tobacco use and expression of EGFR are significant independent predictors of response to erlotinib. Although tobacco use is considered a major cause of NSCLC, other factors are involved in its pathogenesis. In underdeveloped countries such as Mexico, wood and other solid fuels are still used for cooking and heating. The physiopathological mechanisms of wood smoke exposure (WSE) as a potential risk factor for the development of NSCLC are still unknown. Methods: 125 patients with the diagnosis of NSCLC with poor performance status and after first or second-line chemotherapy were treated with erlotinib. Clinical and pathological characteristics were associated with response. Results: We found a global response to erlotinib in 39 patients (31.2%; IC 95% 23–39.3), stable disease in 33.6% and progression in 33.6%. Clinical improvement and favorable changes in status performance were observed in 54.4 and 33.6%, respectively. The clinical features associated with response to erlotinib in the univariate analysis were female gender (44 vs 15.7% p=0.001), non-smokers (45.6 vs 19%, p=0.001), adenocarcinoma (33.8 vs 16% p=0.009) and WSE (81 vs 14% p=0.001). Only the histological type (p=0.049) and WSE (p=0.001) were of statistical significance in the logistic regression analysis. The factors associated to an improved progression-free survival (PFS) in the Cox multivariate analysis were: adenocarcinoma histology (7.6 ±0.7 vs 2.7 ±0.4 months, p=0.002), female gender (7.6 ±1.3 vs 3.97 ±1.5, p=0.027) and WSE (8.43 ±0.5 vs 4.8 ±0.9, p=0.011). Conclusions: Conclusion: WSE is associated with response to erlotinib in patients with NSCLC and may indicate an improved PFS. The EGFR mutation is probably involved in the development of NSCLC in non-smokers with WSE.

No significant financial relationships to disclose.
Single agent bevacizumab and bevacizumab in combination with docetaxel and cisplatin as induction therapy for resectable IB-IIIA non-small cell lung cancer
Authors: Rizvi N. A. , Rusch V. , Zhao B. , Senturk E. , Schwartz L. , Fury M. , Downey R. , Rizk N. , Krug L. , Kris M. G.
Published: March 2020

18045

Background: Bevacizumab (Bev) improves response and survival in patients with advanced non-squamous lung cancer with chemotherapy however there are limited data as single agent therapy and in early stage NSCLC. Methods: Patients with resectable stage IB-IIIA NSCLC were eligible. Patients with adenocarcinoma (Cohort 1) received preoperative Bev and docetaxel and cisplatin (DC). Patients with squamous histology, central location or recent hemoptysis received DC induction therapy without Bev (Cohort 2). Cohort 1 received Bev (15 mg/kg) followed by CT 2 weeks later to assess single agent Bev response. Subsequently D (75 mg/m2) and C (75 mg/m2) were given q 3 weeks; an additional 2 cycles of Bev was administered with C2 and C3 of DC (total of 3 preoperative doses of Bev). Cohort 2 received DC alone followed by resection. Both cohorts received adjuvant Bev x 1 year. Study endpoints included response to single agent Bev, downstaging, safety and survival. Results: 19 patients of planned 70 were enrolled (11 Cohort 1 and 8 Cohort 2). On Cohort 1, there were 2 clinical stage IIB and 9 IIIA patients. After single agent Bev (by bimensional measurement), > 10% reduction in tumor size was observed after 2 weeks in 6/11 patients (- 20%, 15%, 16%, 15%, 13% and 20%). After Bev + DC, there were 6/10 (60%) PRs and DC delivery was 96%. 6/10 patient underwent R0 resection; 1 R2 and 2 were unresectable. 1 patient developed hemoptysis preoperatively and 1 patient developed an upper GI bleed post-operatively. There were otherwise no Bev related operative complications observed. 5/9 patients were downstaged by induction treatment. 3 patients received adjuvant bevacizumab to date (median 5.7 cycles). 8 patients were treated on Cohort 2 (3 with stage IB, 1 with IIB and 4 with IIIA). All 8 patients underwent R0 resection. DC delivery was 94% and there were 6/8 PRs. Downstaging was observed in 5/8 patients and 6/8 are receiving adjuvant Bev (median # cycles to date = 6.7). Conclusions: Bev as a single agent demonstrates regression of tumors after 2 weeks. To date, Bev has been safely administered in the neoadjuvant and adjuvant setting. Preoperative chemotherapy is well tolerated with more than 90% full dose drug delivery. The study is ongoing. Supported by Genentech, Inc.

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