bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pancreatic cancer in breast cancer patients: Incidence and relation with hormone receptor status
Authors: Ghabache B. , Cole J. , Vasireddy S. 
Published: March 2020

17079 Background: There has been a long-standing interest in the role of estrogens in pancreatic tumors and several reports regarding the expression of hormone receptors in pancreatic tumors and the relation between estrogen stimulation and the development of pancreatic cancer have been inconsistent . This raised questions about the increased risk of pancreatic cancer among breast cancer survivors and the possible role of antihormonal therapy in the prevention and treatment of these malignancies. Methods: The Tumor registry at the Ochsner Clinic Foundation in New Orleans was queried to identify new cases of pancreatic cancer among patients previously diagnosed with breast cancer. This was done by matching data on pancreatic and breast cancer diagnosed between January 1996 and January 2006. For each case of pancreatic cancer, data was collected from the initial breast cancer pathology report, this included : Cancer type, Grade, Estrogen Receptor status, Progesterone Receptor, HER- 2 Receptor status , BRCA gene mutation and cancer stage on diagnosis. Clinic notes and radiology reports were also reviewed to determine the presence of risk factors for pancreatic cancer, the interval of time between the two diagnosis and the stage of breast cancer at the time of diagnosis of pancreatic cancer. Results: A total of 2,669 breast cancer cases were reviewed and 5 cases of pancreatic cancers were found among patients with a previous diagnosis of breast cancer. In all these cases the breast cancer tumor was positive for Estrogen and Progesteron receptor and negative for Her2 overexpression. The incidence of pancreatic cancer in this subgroup of patients (Breast cancer, ER+,PR+, HER2-) was 1% much higher than the incidence in the general female population. Conclusions: In our experience patients with breast cancer might have a higher risk of developping pancreatic cancer. This is especially true for patients whose tumors over-express the estrogen and progesterone receptors and which do not over-express the Her2 receptor. Further studies are needed to evaluate the overall incidence of pancreatic cancer in this population and to determine the role of anti-hotmonal therapy in the prevention of these cancers. No significant financial relationships to disclose.
Pleural effusions in patients treated with dasatinib: Results from two institutions, risk factors and management
Authors: Lipton J. H. , Sriharsha L. , Bogomilsky S. , Casciaro L. , Keating A. , Messner H. , Laneuville P. 
Published: March 2020

17503 Background: Dasatinib (SPRYCEL, formerly BMS354825) is a multi-targeted kinase inhibitor that has been shown to be very effective in the therapy of imatinib-resistant and -intolerant Ph-positive CML/ALL patients, frequently resulting in hematologic and cytogenetic remissions. Therapy with kinase inhibitors has been limited to some extent by fluid retention, the type of which is dependent on the individual drug. Pleural effusions have been relatively more common with dasatinib. We report on the experience at two large teaching hospitals - incidence, risk factors and management. Methods: 27 patients were treated on 5 BMS Phase 2 Studies (2CP, 1AP, 1BP-M, 1BP-L, 1ALL) - 17 CP, 5 AP, 3 BP-M, 2 BP-L/ALL. All patients started on a dose of 70mg BID of dasatinib. Results: In all 13 patients developed effusions. All but 1 were Grade 2; grades 2–4 are symptomatic and require intervention. Of the 14 who did not, 9 were either withdrawn from study because of CML progression (3) or dose-reduced because of hematological toxicity (6). The development of effusions was more common in patients with more advanced disease (BC>AP>CP), in those with previous lung problems (smoking, infections), and in those maintained on starting doses of dasatinib. Effusions could develop even 1–2 years (1>100d, 2>200, 2>300d, 1>500d) after starting therapy often triggered by a lung infection. Effective management included ongoing combinations of diuretics, temporary drug discontinuation, dose reduction, and more recently a once daily drug dosing schedule (Hochhaus et al , Blood 2006, 108: 166a). One patient required thoracentesis and chest tube. Conclusions: Dose monitoring and adjustments and management of the effusions have permitted continuation of the therapy in 10 of the 13 patients with good hematological outcomes. A change in dose schedule will be most effective. No significant financial relationships to disclose.
High-dose chemotherapy followed by autologous stem-cell transplantation for Hodgkin disease using CVB as conditioning regimen
Authors: Avila R. A. , Valdéz J. A. , Caeiro G. , Basquiera A. L. , Sturich A. G. , Berretta A. R. , García J. J. 
Published: March 2020

17505 Background: Autologous stem-cell transplantation has become a widely used therapy in Hodgkin's disease. We analysed outcome, overall survival (OS) and time to progression (TTP) in relapsed patients with Hodgkin's disease undergoing autologous stem-cell transplantation (ASCT) in a single institution. Methods: Between 1996 and 2006, 28 patients (19 males and 9 females; median age 31 years old, range 10–63) underwent high dose chemotherapy with CVB regimen (cyclophosphamide 6 gr/m2, VP-16 2.400 mg/m2, and BCNU 450 mg/m2) with autologous stem-cell support. Before transplantation, 20 patients had received two lines of chemotherapy and 8 patients, three lines or more. At time of transplantation 12 (42.8%) patients were in complete remission and 16 (57.2%) in partial remission after rescue chemotherapy. The graft consisted of bone marrow (n: 6) or peripheral blood stem cells (n: 22). Results: The 100-day mortality rate was 3.57 %. With a median follow-up of 36 months for the surviving cohort, the median time of TTP and OS was of 31.4 and 55.63 months respectively and the five years TTP and OS were of 45% and 47% respectively. The most common toxicities presented were febrile neutropenia (100%) and mucositis (92%), both of them resolved completely before discharged. Patients who achieved complete response (n=20) after transplantation (evaluated at 100-day) had a better OS than patients who achieved partial response (n=8) (HR: 0.11; CI: 95% 0.03–0.49; p:0. 0036). Conclusions: High dose chemotherapy using CBV as conditioning regimen followed by ASCT is an effective treatment to achieve complete remission, which is associated with better survival in our series. This regimen presented acceptable toxicity and low mortality. No significant financial relationships to disclose.
Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) following treatment for ovarian cancer
Authors: Gupta B. , Sait S. N. , Block A. W. , Ford L. A. , Moysich K. B. , Baer M. R. 
Published: March 2020

17506 Background: Therapy-related AML (t-AML) has been reported in ovarian cancer patients treated with chemotherapy and has been associated with the use of platinum. However, little is known about these patients’ clinical characteristics, cytogenetic changes, clinical course or treatment outcome. Methods: Roswell Park Cancer Institute patients with diagnoses of AML or MDS by French-American- British (FAB) Group or World Health Organization criteria following a diagnosis of ovarian cancer were retrospectively reviewed. Results: Ten patients were identified between 1990 and 2006. All 10 had received platinum chemotherapy, and 8 (80%) had also received taxanes, 4 (40%) cyclophosphamide and 3 (30%) adriamycin. The median age at ovarian cancer diagnosis was 56 (range, 49–78) years, and the median age at AML/MDS diagnosis was 62 (range, 56–81) years. The median interval from diagnosis of ovarian cancer to AML/MDS was 5.5 (range, 3–11) years, while the median survival time of 395 ovarian cancer patients treated at RPCI between 1982 and 1998 was 4.1 years (range, 1 month to 23 years). Eight patients had AML and 2 had MDS. AML FAB types were M2 in 3, M0 and M4 in 2 each, and M6 in 1. Among 9 patients with cytogenetic data available, 6 had complex karyotypes, all of which included monosomy 5 or del(5q), and three had single clonal abnormalities, all involving chromosome 7. Of 7 AML patients who received induction chemotherapy, only 3 achieved complete remissions, and remissions were brief (3, 4.5 and 5 months). Median overall survival for all ten patients after diagnosis of AML or MDS was 4 months (range, 0.5 months to 9.5 months). Conclusions: Patients with t-AML/t-MDS following therapy for ovarian cancer have unfavorable cytogenetic abnormalities, including complex karyotypes and involvement of chromosomes 5 and 7, which are typical findings following alkylating agent therapy, and these patients have a very poor prognosis. No significant financial relationships to disclose.
Phase I study of nilotinib in patients (pts) from Japan with imatinib-resistant Ph+ chronic myelogenous leukemia (CML) or acute lymphocytic leukemia (ALL)
Authors: Tojyo A. , Miyazaki Y. , Usui N. , Kobyashi Y. , Okamoto S. , Oyashiki K. , Nishimura M. , Okada M. , Natori H. , Tanii H. 
Published: March 2020

17511 Background: Nilotinib is a highly selective Bcr-Abl tyrosine kinase inhibitor designed to be more potent than imatinib. Results from a phase I study in Japanese pts with imatinib-resistant/intolerant Ph+CML/ALL are reported. Methods: Japanese pts with imatinib-resistant/intolerant Ph+CML (5 CP; 2 AP; 2 BC) or ALL (2) were enrolled in an open-label, dose-escalation study evaluating safety, efficacy and pharmacokinetics (PK) of oral nilotinib. A standard three-pt-per-cohort design was used; initial cohorts included 200mg QD, 400mg QD, and 400mg BID. Serum samples were collected on days 1 and 15 of cycle 1 in all 11 pts. Results: Peak serum concentration was achieved at 4 hrs in most pts. Systemic exposure increased with dose. Serum level reached steady-state within 1 week and was stable over time. The accumulation ratio (AUC day15/day1) was 2 to 3. Nilotinib 400mg BID maintained serum levels >/= 30 times higher than the IC50 required to inhibit Bcr-Abl phosphorylation. No pt experienced dose-limiting toxicity. 7/11 pts had Grade 3/4 AEs, only 1 pt had an AE (thrombocytopenia) suspected as being related to nilotinib treatment. No pt had EKG abnormalities. 57% of all pts and 75% of CML CP pts achieved MCyR. 3 pts in the 200mg QD cohort discontinued due to disease progression, all other pts completed the study. PK results are summarized in Table 1 . Conclusions: Nilotinib PK profile in Japanese pts is comparable to that reported for pts outside Japan. Based on these data, the recommended starting dose of nilotinib in Japanese pts with imatinib-resistant/intolerant Ph+ CML/ALL is 400mg BID. [Table: see text] No significant financial relationships to disclose.
Molecular remission to imatinib-IFN-alpha combination or imatinib monotherapy in chronic myeloid leukemia (CML) patients
Authors: Liberati A. , Schippa M. , Luzi D. , Falchi L. , Emili R. , Capparella V. , Cerroni P. , Gentileschi E. , Gottardi E. , Saglio G. 
Published: March 2020

17512 Background: Continously improving results have been obtained in the control of Philadelphia chromosome (Ph’) positive CML. However, the final goal of molecular remission remains difficult to be obtained, even in the imatinib era. Evaluation of the rate of complete molecular remission (undetectable p210 transcript at RQ-PCR confirmed by NESTED/RT-PCR in at least two subsequent tests over a period of 3 mths or more) to imatinib or to imatinib-IFNa combination as first, second or subsequent line of therapy. Imatinib alone or in combination with IFNa was given as first, second or subsequent line of therapy to a total of 47 patients. In particular, 21 patients were treated at the time of diagnosis with imatinib alone (18,G1) or imatinib-pegilated IFN combination (3,G2). Twenty-three additional patients (G3) received imatinib as second line therapy. Finally, 13 patients were treated with the imatinib-IFNa combination as second (7,G4) or third (6,G5) line therapy, but in two cases IFNa was discontinuated after one month because of intolerance to treatment. Methods: Molecular response was evaluated by NESTED/RT-PCR (Guo JQ et al.; Leukemia:2002;15:2447–53) and RQ-PCR (Gabert J et al. Leukemia:2003;17:2318–57) at time intervals of 3–6 months from the beginning of therapy. Results: Complete molecular remission lasting 3 months or more (range 3–34) was obtained in 15 of 44 evaluable patients (therapy duration = 11 mths, range 11–73).The response rate was higher in patients receiving imatinib- IFNa combination given as first or second line therapy (5/13) than in those given imatinib monotherapy (9/37). In 7 of the 15 complete responders, remission duration lasted more than 12 mths (range 12–34) with 6/7 pts still continuous remission. In further 6 cases continuous remission duration ranged from 3–8 mths while in one case fluctuating negative-positive NESTED/RT-PCR tests have been observed over a period of 65 months. Conclusions: It is not possible to draw any firm conclusion regarding the effect of the imatinib-INFa combination on molecular response because of the small sample size of treated patients. However, our findings suggest an additive effect of imatinib and IFNa in Ph’positive clone control. No significant financial relationships to disclose.
Allogeneic stem cell transplantation (allo-SCT) in adult acute lymphoblastic leukemia (ALL)
Authors: Wu S. J. , Yao M. , Tang J. L. , Chen Y. C. , Cheng A. L. , Tien H. F. 
Published: March 2020

17513 Background: Although viewed as a potentially curable disease, the outcome of adult ALL is extremely poor. The role of allo-SCT, a possible curative modality, is of debate. Although the solid evidence is lacking, allo-SCT is viewed as a standard treatment in some institutions and some trials. The objective of the study is to clarify the effect of allo-SCT in the treatment of adult ALL patietns. Methods: From Jan. 1999 to Jun. 2006, we included 103 adult ALL patients whose age were between 15 and 55, the upper limit of age for allo-SCT in this institution. Their data, including clinical characteristics, cytogenetic results, treatment response and outcomes, were collected. To avoid the “immortal-time bias” in assessing the effect of transplant, the results from a time-independent and time-dependent Cox proportional hazards model were compared. We also conducted a population-based study to compare the outcomes of these patients with those diagnosed between Jan. 1986 and Dec.1993 in our institution. Results: There were 46 females and 57 males. The median age was 25.8, with 63 patients (61.2%) younger than 30. The median survival was 21.9 months and the 3-year overall survival was 34.2%. 48 patients(46.6%) received allo-SCT. The transplant conferred to marginally better survival in univariate analysis (p=0.049), but by time-dependent regression method, there was, after adjusting for other risk factors, no survival benefit for patients receiving transplant (HR 1.452, 95% CI 0.766∼2,751, p=0.253). The outcomes of these 103 patients were compared with another group of 69 patients diagnosed in the early period, among whom 13 patients(18.8%) received transplant. Although with higher proportion of patients undergoing allo- SCT, there was no advance in overall survival (p=0.157). Conclusions: In adult ALL, the outcome is still poor. Although there are new treatment protocols and modalities in chemotherapy and transplantation, these advances do not reflect to survival improvement. Transplantation provides limited survival benefit in population-based viewpoint. The candidates of allo-SCT should thus be carefully selected and allo-SCT should not be viewed as a standard in the treatment of adult ALL patients. No significant financial relationships to disclose.
Prognostic factors in Chinese patients with chronic lymphocytic leukemia
Authors: XU W. , Li J. , Zhang S. , Wu Y. , Zhu Y. , Zhu Y. 
Published: March 2020

17518 Background: Recently, some new factors, such as cytogenetic abnormalities, ZAP-70, proliferative antigen Ki-67, and the expression of CD38 in leukaemic cells, were strong indicator of prognosis in B-cell chronic lymphocytic leukaemia (B-CLL). The aim of this study was to explore the characteristics of molecular cytogenetics in Chinese patients with CLL, evaluate the expression of Ki-67, ZAP-70 and CD38 in leukaemic cells, and analyze the influence of factors on the prognosis of CLL. Methods: Interphase fluorescence in situ hybridization (FISH) was used to detect cytogenetic aberrations, and a panel of FISH probes for 13q14 (D13S319), 17p13 (p53 gene), 11q23 (ATM gene), the centromere of chromosome 12 (D12Z3) and 14q32 (IGHC/IGHV) was applied on bone marrow or peripheral blood smears from 52 Chinese B-CLL patients; Four-color flow cytometry was used to determined the expression of ZAP-70 protein and CD38; Immunohistochemistry was applied to measure the expression of Ki-67 antigen and Bcl-2 protein. Kaplan-Meier was used for survival time. Results: Out of the 52 patients, 42 (80.7%) had at least one kind of molecular cytogenetic aberration and 16 (30.8%) with 2 abnormalities. The most frequent abnormalities detected in our patients was deletions of 13q14 in 26 cases (50.0%), followed by trisomy of chromosome 12 in 11 patients (21.2%), deletions of 17p13 in 10 patients (19.2%), deletions of 11q23 in 6 patients (11.5%), and 14q32 translocation in 5 patients (9.6%). Fourteen patients (26.9%) were positive for ZAP-70 (=20%), and 13 patients (25.0%) were positive for CD38. Positive ZAP-70 and CD38 status was associated with advanced disease stage (Binet C). The expression levels of Ki-67 in Binet C stage was higher than that in early stage (Binet A and B). In univariate analysis for survival, 13q14 deletion was a favorable prognostic factor, and the deletions of 17p13 and 11q23 were poor prognostic factors. The survival time was longer in the group with lower expression of Ki-67 than that in the higher expression group. Both ZAP-70 and CD38 expression were shown to predict the clinical course of the disease. Conclusions: Chromosomal aberrations (deletions of 13q14, 17p13 and 11q23), and expression of Ki-67, ZAP-70 and CD38 have been shown highly predictive prognostic value for Chinese patients with B-CLL. No significant financial relationships to disclose.
Hypereosinophilic syndromes (HESs) variable clinical presentations and responses to treatment
Authors: Mitra S. , Power D. , Thornton P. D. , O Donnell R. , Murphy P. T. 
Published: March 2020

17529 Background: Hypereosinophilic syndromes (HESs) refers to a heterogenous group of disorders characterised by marked blood eosinophilia (>1500/cu mm) and tissue eosinophilia (lasting for more than 6 months), in the absence of other eitiologies for eosinophilia, resulting in end organ damage. Eosinophilias may be reactive or due to a chronic myeloproliferative disorder (with evidence of clonal proliferation).Clonal eosinophilias are very often associated with the fusion gene FIP1L1-PDGFR alpha which causes the generation of a constitutively active Tyrosine Kinase. Treatment modalities for HES includes corticosteroids, chemotherapeutic agents, alpha- interferon, tyrosine kinase inhibitors (eg Imatinib mesylate) and the monoclonal anti-interleukin 5. Patients carrying FIP1L1-PDGFRalpha respond very well to Imatinib. Aim:Retrospective review of the variable response of 7 patients with HES (over a period of 6 months), to current treatment modalities. Methods: The 7 patients (6 Male, 1 Female; age range 37–80 yrs; mean age 56 yr) presented with eosinophilia in the range 2600–73,000 /cu mm.They were followed up for >6 months. A response to treatment was defined as Eosinophil count<1500 /cumm or Eosinophil count < 5% of the total leucocyte count .Four of the 7 patients received Imatinib as initial treatment. Two patient initially had steroids followed by Imatinib and 1 patient (aged 80 yr) was treated with Hydroxyurea initially. Results: Four of the 6 patients receiving Imatinib responded to it. Of the 2 patients not responding to Imatinib,1 responded partially to Hydroxyurea and the other did not respond to monotherapy with steroid or alpha-interferon (but eventually responded to a combination of the two). The patient who had initial treatment with Hydroxyurea responded well. Of the 7 patients 1 was positive for the FIP1L1-PDGFRalpha fusion gene,1 result was equivocal, 3 were negative and 2 were not tested (not available at the time). Of the 2 that were negative,1 responded to Imatinib. Conclusions: Response of HES patients to the various treatment modalities, is variable and often unpredictable.The FIP1L1-PDGFR alpha fusion gene is not often present;however other Tyrosine Kinases may be dysregulated and hence a trial of Imatinib is worth considering in most cases. No significant financial relationships to disclose.
Outcome of patients of CML in AP and BC with imatinib: A retrospective analysis of patients from India
Authors: Menon H. , Hingmire S. S. , Bharath R. , Jain K. , Ghadyalpatil N. , Prasad N. , Biswas G. , Deshmukh C. , Sastry P. , Parikh P. M. 
Published: March 2020

17531 Background: Imatinib is a very active agent in advanced phase CML. The present study assesses the impact of Imatinib therapy on the outcome of Indian patients with CML in Accelerated Phase (AP) and Blast Crisis (BC). Methods: Patients of CML in AP or BC who were treated with Imatinib based therapy between 2001 and 2006 were analyzed retrospectively. Results: A total of 65 patients who received Imatinib based treatment for CML in AP or BC were analyzed. Thirty eight (58.46 %) patients diagnosed in chronic phase (CP) were initiated on Imatinib based treatment at time of progression to AP or BC. The remaining 27 (41.53 %) patients had AP or BC of CML at initial diagnosis. At the time of start of Imatinib treatment 36 (55.38 %) patients had AP and 29 (44.61 %) were in BC. Imatinib as a single agent was used in 41 (63.07 %) patients (27 in AP and 14 in BC) and in combination with oral 6-MP and Etoposide was used in 24 (36.92 %) patients (14 in AP and 10 in BC). Hematological response (HR) was seen in 64.61% (42 out of 65) patients, complete HR in 32 (49.23 %) and partial HR in 10 (15.38 %). Cytogenetic response (CR) was noted in 21 (32.31%) patients (Complete -10, Partial -9, and Minor - 2). Twenty eight (43.07%) patients remained progression free (HR+CR in 16 and only HR in 12 patients) till the last date of follow up (median duration of follow-up was 17 months).For the whole group (n=65) the overall survival from the diagnosis of AP or BC after commencing Imatinib treatment was 65.3%, 51.6% and 34.4% at 1, 2 and 3 years respectively. The median survival was 25 months. The median survival and OS at 1 year, as expected, was significantly better for patients in AP (36 months, 77.4 %) as compared to those in BC (11 months, 48.2%)(p=0.004) and both were much longer than previously reported with non-Imatinib therapy. Outcome in patients with AP or BC was not significantly improved by addition of 6-MP and Etoposide. Temporary discontinuation of Imatinb for grade III/IV toxicity was done in 27 (41.53 %) patients for a median duration of 28 days. Conclusions: Imatinib has improved the outcome of patients with advanced phase CML. Our data also documents this in patients from India. However, Imatinib needs to be studied with newer combinations to achieve long term disease control in patients with CML, particularly those in BC. No significant financial relationships to disclose.