bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pilot Study of Low Dose Melphalan and Bortezomib for Treatment of Acute Myelogenous Leukemia and High-Risk Myelodysplastic Syndromes.
Authors: Bubis Jeffrey A. , Ely Pamela , Meehan Kenneth R. , Stearns Diane , Schaal Anna D. , Kimtis Elizabeth A. , Lowrey Christopher , Bengtson Elizabeth M. , Hill John , Gautier Marc 
Published: October 2019

Abstract
Elderly patients with AML (>60) have a poor prognosis due to high risk cytogenetics and a high incidence of secondary AML. Comorbid conditions make induction therapy more risky and less effective. There is a need for less toxic and more effective treatment for these patients. The combination of bortezomib (B) and melphalan (M) demonstrate synergistic cytotoxicity in vitro against AML cell lines providing a rationale for this combination in patients with AML. We report the initial results of a pilot study of low-dose M and B for the treatment of patients with AML and high-risk myelodysplastic syndromes. Eligibility requirements included a diagnosis of AML or high-risk MDS and subjects were not candidates for standard induction therapy or had failed therapy. Strata 1 included patients who had received no previous therapy and strata 2 patients with refractory or relapsed disease. Treatment consisted of M (2mg) oral daily dose and B (1.0mg/M2) on day 1, 4, 8 &11 of a 28 day cycle. Ten patients have been enrolled. Median age was 69 (range 54–79), 8 patients w/ AML and 2 w/ refractory MDS. Five patients were previously treated (strata 2); regimens included induction (7(3), auto SCT (1) and azacytadine (2). Cytogenetic abnormalities were present in 70% of patient specimens. To date 25 cycles of treatment have been given (range 1–6). Six patients are evaluable for response. Two patients (both with MDS) were withdrawn after 1 cycle for cytopenias. Two patients with AML achieved CR by bone marrow morphology. One patient, a 78 year old man with multiple cytogenetic abnormalities and no previous treatment achieved remission with normalization of cytogentetics after 4 cycles. A 74 year old man who had failed previous therapy for his AML achieved a morphologic remission with persistent cytogenetic abnormalities after 6 cycles. Three patients required admission for management of febrile episodes in association with neutropenia that were disease related. There were no treatment related admissions or grade 3/4 non hematologic toxicity events. The 74 year old man who achieved a CR with no “in hospital” days while on study had previously failed to respond to two induction attempts which required a 44 day hospitalization. Accrual continues. In summary, the combination of low dose oral melphalan with low dose bortezomib appears to be a novel, active and well tolerated outpatient treatment for elderly patients with high risk MDS and AML.
A Phase I Study of the Histone Deacetylase Inhibitor MGCD0103 (MG-0103) Given as a Three-Times Weekly Oral Dose in Patients with Leukemia or Myelodysplastic Syndromes (MDS).
Authors: Garcia-Manero Guillermo , Minden Mark , Estrov Zeev , Verstovsek Srdan , Fiorentino Jackie , Kantarjian Hagop , Reid Gregory , Martell Robert E. 
Published: October 2019

Abstract
MG-0103 is a novel non-hydroxamic acid inhibitor of human histone deacetylases (HDACs), with selectivity for the cancer-associated isoforms of class I HDACs. Deacetylation of histones by HDACs is postulated to inactivate tumour suppressor genes leading to neoplastic transformation, and therefore inhibition of this enzyme may result in antineoplastic activity. To study the safety and activity of MG-0103, we have developed a phase I open-label dose escalation study of MG-0103 administered orally, three-times weekly in patients with leukemia or MDS, with the primary endpoints being the determination of the maximum tolerated dose (MTD) and the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of MG-0103. Eligibility criteria included appropriate performance status and renal and hepatic functions. Patients with relapsed/refractory leukemia or MDS and older patients with untreated AML/MDS were eligible. Eight patients have been enrolled at two dose levels (20 &40 mg/m2) so far. Their characteristics are: median age 70 years (range 33–79); all patients so far treated have AML; median number of prior therapies is 1 (range 0–3). All patients had complex cytogenetics including one elderly patient with t(8;21) that had not achieved CR with high dose ara-C-based therapy. MG-0103 has been well tolerated with no dose-limiting toxicities. No drug-related adverse events (AEs) >= Grade (Gr) 3 have been observed. The only Gr 2 drug-related AE has been heartburn (1 patient). All other drug-related AEs were grade 1. No cardiac abnormalities have been observed so far. Two of 3 patients at the first dose level have been treated for 3 or more cycles. PK evaluations are shown in the table below. Analysis of peripheral blood cell HDAC activity indicates that HDAC inhibition occurs in a dose-dependent manner. Enrolment is currently proceeding at a dose of 80 mg/m2. In summary, MG-0103 is a well-tolerated HDAC inhibitor in patients with AML at doses and exposures that result in target inhibition in peripheral blood.
Dose 20 mg/m2 40 mg/m2 Pharmacokinectic characteristics AUC (0-∞) ng.hr/ml 260 +/− 10.8 528 +/−275 T 1/2 h 8.09 +/− 2.98 6.24 +/− 0.373
Acute Myeloid Leukemia in the Elderly, Intensive or Maintenance Therapy? Our Experience in Patients over 65 Years.
Authors: Mettivier Vincenzo , Pezzullo Luca , Rocco Stefano , Finizio Olimpia , Bene Lucia , De Rosa Carlo , Nunziata Giuseppe Rodolfo , Liberati Marina 
Published: October 2019

Abstract
The treatment of acute myeloid leukemia in elderly with age > 65 years is still debated. Various reported studies have valued the feasibility of intensive chemotherapy in these setting of patients. The aim of the our study is to value the difference in DFS and OS among 2 groups of elderly patients with AML treated with intensive chemotherapy (IC) or maintenance (M). From June 2001 to May 2005 we have accepted in our Division 45 patients affected by AML aged up to 65 years. 25 were male and 20 were female, with a median age of 75 years (range 67–86 years). 22 patients (12 M and 10 F, median age: 71 years) received intensive chemotherapy (I.C. Flag and MICE) and 23 (13 M and 10 F, median age: 78 years) received or maintenance therapy (low dose cytarabine) or only support. In IC group 11 patients (50%) have obtained to complete remission (CR) with a DSF and OS media of 7,5 and 6,3 months respectively, and a TRM rate of 27%. In the M group the CR has been documented in 6 patients (35%) treated with low dose of cytarabine, with a DFS and OS media of 6,9 and 4,4 months respectively (graph 1–2). This results have shown, as expected, a better CR rate in the IC group, but without any advantage in terms of OS and DFS when compared with the M group. Difference is not statistically significant between the two groups (p: 0.5). Despite a good CR rate, Intensive chemotherapy do not improves survival in elderly patients. This is probably due to the combination of either a high TRM in patients treated with intensive chemotherapy or a high relapse rate. New therapeutics strategies are needed to improve DFS and OS in these patients. Interesting is the use of specific monoclonal antibodies (anti CD33) in this poor risk disease especially in maintenance after a CR obtainable with a low intensive or low dose chemotherapy.
Figure Figure
Treatment of Children with Relapsed Acute Myeloid Leukemia with Gemtuzumab in Combination with Mitoxantrone and Cytarabine.
Authors: Aplenc Richard , Alonzo Todd A. , Gerbing Robert , Smith Franklin O. , Eric Sievers , Arceci Robert J. 
Published: October 2019

Abstract
Despite improvements in the treatment of children with de novo acute myeloid leukemia (AML), a substantial fraction of patients experience relapse. The Children’s Oncology Group Phase I trial, AAML00P2, sought to test the safety and feasibility of combining Gemtuzumab (GMTZ) with a standard AML reinduction regimen of mitoxantrone and cytarabine in a dose de-escalation design. Patients received cytarabine 1000 mg/m2/dose every 12 hours on days 1–4 with mitoxantrone 12 mg/m2/dose daily on days 3–6. The starting dose of GMTZ for dose finding was 3 mg/m2 once on day 7. Doses for patients under 3 years of age were as follows: cytarabine 33 mg/kg/dose, mitoxantrone 0.4 mg/kg/dose, and GMTZ 0.1 mg/kg/dose. Three patients were enrolled in the dose finding strata and an additional 18 patients were subsequently enrolled to acquire further toxicity data. Of these, 15 were male and 6 female. The median patient age was 11.3 years, range 1.2 to 19.2 years. No patients in the initial dose finding cohort experienced a dose limiting toxicity. Toxicities observed in the entire cohort of 21 patients included hematologic and infectious complications typical of AML therapy. One patient had grade III bilirubin elevation. No patients had grade III or IV hepatic toxicity or grade III or IV veno-occlusive disease (VOD). Data on toxicity in stem cell transplant post GMTZ exposure is limited. However, no episodes of VOD have been reported. In summary, GMTZ combined with cytarabine and mitoxantrone is reasonably well tolerated in pediatric AML patients.
Subclincal Atherosclerosis as Measured by CIMT Is Present in Patients with Hodgkin’s Disease.
Authors: Levine Jennifer M. , Weiner Michael A. , Rundek Tatjana , Elkind Mitchell S.V. , Hughes Deborah , Ramas Romel , Cheung Ken , Kelly Kara M. 
Published: October 2019

Abstract
Cardiovascular disease is a well-described late effect of treatment for Hodgkin’s Disease (HD), generally attributed to high dose radiation therapy (RT) to the mediastinum and neck. Increased carotid artery intima-media thickness (CIMT), measured by ultrasound, is a valid marker of subclinical atherosclerosis and is associated with an increased risk of future vascular disease. We evaluated CIMT in 31 patients with HD, (22 males, 9 females), mean age 21 (range 9–39) years, between 2 and 241 months from diagnosis. Thirty patients received chemotherapy, including anthracyclines. Sixteen patients were treated with RT to the bilateral neck and mediastinum; 4 received high dose (36Gy) RT and 12 received lower dose (21–25Gy) RT. One patient received lower dose RT only to the bilateral neck. Fourteen patients were treated with chemotherapy alone. CIMT was assessed using a standardized scanning and reading protocol. The CIMT was calculated as the mean of the maximum measurement at 12 sites; near and far walls of the common carotid, bifurcation and internal carotid arteries bilaterally. The mean CIMT for the total cohort was 0.757mm. Among 5 patients (mean age 13, range 9–16 years), evaluated while actively receiving therapy or within one year from completion of therapy, mean CIMT was 0.715, equivalent to the mean CIMT found in healthy 30 year old adults (Stein, Stroke 2004). In a multivariate linear regression analysis CIMT was significantly associated with increasing time since diagnosis (p=0.035), age (p=0.016), and male gender (p=0.014). There was no difference in CIMT between those patients treated with chemotherapy alone vs. chemotherapy and radiation therapy. Subclinical atherosclerosis in patients with HD may evolve early in the course of treatment and survivorship and then increase with age and time from diagnosis. Type of treatment was not a significant predictor of CIMT in our cohort suggesting that factors other than RT play a role in the development of subclinical atherosclerosis. Further studies are needed to better elucidate the etiology of atherosclerotic disease in HD survivors. Screening with CIMT may detect subclinical atherosclerosis and allow for earlier intervention to prevent cardiovascular disease in this population.
Analysis of Clinical Characteristics and Prognostic Variables of Hodgkin’s Lymphoma: A Single Center Experience.
Authors: ALshemmari Salem H. , Bhat Ganapathi M. , Ameen Reem M. , Sajinani Kamlesh P. , Gyarfas Jan 
Published: October 2019

Abstract
Background: Hodgkin’s disease is a curable malignant disease. Despite advances in the management of this disease entity, there are groups of patients who suffer relapse and identification of prognostic variables and adaptation of treatment to individual risk remains a major challenge. Emphasized in this study are the clinicopathological characteristics and outcome of Hodgkin’s lymphomas.
Materials and Methods: A retrospective analysis of 245 adult patients treated for Hodgkin’s lymphoma between October 1990 and Dec 2004 was done. An analysis of the most important variables was made in terms of both disease free and overall survival. Spectrums of pretreatment factors were evaluated including International Prognostic Factors, extranodal disease symptoms, histology, and bulky disease. Patients were treated with chemotherapy, radiotherapy either alone or in combinations at the beginning and relapses was treated with various salvage regimes combined with radiotherapy and stem cell transplant.
Results: The median age in this study group was 32 years (14–72) and 156(63.67%) were male. Distribution by stages were: stage I-43, stage II-113, stage III-44, and stage IV-45.Pathological subtypes were Nodular sclerosis-128, Mixed cellularity-56,Lymphocyte rich classical-13,Lymphocyte depletion-7,and nodular lymphocyte predominance-29,not specified in 12.B symptoms observed in 95,bulky in 72 and Extra nodal involvement in 63 patients. Complete remission was achieved in 226 patients with first line management (92.24%).Primary chemo refractory (19) and relapses were observed in 72 patients, and subsequent salvage chemotherapy including stem cell transplant (28 patients) resulted CR in 41.With the median follow up of 41months (1-374), OS was 95% and DFS was 87%.Twelve patients died out of which 8 due to disease recurrence or progression.
Conclusions: Achieving a complete remission shows a favorable prognosis for prolonged DFS. StageIV, bulky disease,B symptoms, extra nodal involvement and NS histology were associated with inferior OS and DFS. Additional factors for poor DFS were male sex, hypoalbumenemia and anemia. Age and leucocytosis did not affect the outcome. Identifying the pretreatment risk factors may be useful in designing clinical trials for the treatment of relapsed and refractory Hodgkin’s disease and in making individual therapeutic decisions.
Flow Cytometry and Fluorescence In Situ Hybridization Are Methods of Choice for Routine Diagnosis of Mantle Cell Lymphoma.
Authors: Rymkiewicz Grzegorz , Woroniecka Renata , Blachnio Katarzyna , Pienkowska-Grela Barbara , Walewski Jan 
Published: October 2019

Abstract
Mantle cell lymphoma (MCL) is a distinct clinicopathologic entity, characterized by expansion of lymphocytes with co-expression of CD5 and CD20 and frequent t(11;14) translocation. MCL and its morphological variants are frequently confused with other lymphoma subtypes. The aim of this study was to analyze a contribution of histopathology (HP), immunohistochemistry (IHC), flow cytometry (FCM) and cytogenetic analysis with fluorescence in situ hybridization (FISH) to ultimate diagnosis of MCL. We identified 66 pts diagnosed with MCL either by use of HP/IHC or/and FCM. Initial diagnosis was based on HP/IHC only, and was validated in 55 of 66 patients by combined use of HP/IH, FCM, and FISH. We examined paraffin sections IHC panel consisting of antibodies to CD3, CD5, CD20, CD23, CD43, and cyclin D1. FCM analysis was done by 3-colour direct immunofluorescence with extended panel of antibodies to CD5, CD10, CD11c, CD19, CD20, CD22, CD23, CD25, CD38, CD45, HLADR, FMC7, light and heavy chains. We used FISH to detect the t(11;14) in interphase cells of 24 cases of MCL. All 55 cases of MCL were CD20 positive and CD23 negative on IHC, 32 of 51 (63%) and 46 of 52 (88%) cases coexpressed the CD5 and CD43 antigens, respectively. Cyclin-D1 staining revealed nuclear positivity in 38 of 52 (73%) pts. Dual expression of CD5 and cyclin D1 - a finding highly reliable for MCL diagnosis on IHC, was seen in 49% (27/55) of pts. All MCL cases were CD20 (51/51) and CD19 (55/55) positive by FCM with higher intensity of CD20 expression compared to CD19 in 100% (51/51) of cases. CD5 and CD25 were coexpressed in 54 of 55 (98%) and in 43 of 49 (88%) pts respectively. CD22 (45/45) and HLADR (55/55) were positive in all cases. FMC7 and CD38 were found in 22 of 23 (96%) and in 19 of 23 (83%) patients, respectively. CD10, CD11c, CD23 were only seen on a subpopulation of cells with weak intensity in 15%(7/48), 13% (6/45), and 11% (5/46) pts., respectively. MCL cells expressed moderate intensity monoclonal surface light chains in 47 of 52 (90%) pts with L light chain predominance and IgM+/IgD+ in 16 of 17 (94%) pts. False or incomplete initial diagnosis based mainly on lymph node HP/IHC was found in 35 of 66 (53%) cases. False FCM diagnosis of MCL was found in 2 of 66 (3%) cases. Results of FCM and FISH were consistent with the MCL diagnosis in 92% (22/24) of patients, in our hands. Our data indicate that the phenotypic pattern of MCL by FCM is remarkably constant among patients. As MCL represents a frequent diagnostic challenge, a combined use of FCM and FISH may provide an optimum solution.
Gastrointestinal Involvement in Mantle Cell Lymphoma (MCL). A Prospective Clinical, Endoscopical, Pathological and Molecular Study.
Authors: Salar Antonio , Juanpere Nuria , Gonzalez-Barca Eva , Bellosillo Beatriz , Espinet Blanca , Seoane Agustin , Panadés Agustin , Romagosa Vicente , Pedro Carmen , Nieto Miguel , Abella Eugenia , Domingo-Domenech Eva , Sole Francesc , Fernandez-Sevilla Alberto , Besses Carlos , Serrano Sergio 
Published: October 2019

Abstract
Objective: to investigate the clinical, endoscopical, microscopical and molecular involvement of the GI tract in a prospective series of MCL.
Methods: 13 patients with MCL have been prospectively and consecutively entered in a staging workup that included upper and lower endoscopy of the GI tract. Multiple biopsies of the stomach and colon were taken from pathologic mucosa and also from macroscopically normal mucosa. Specimens were assessed with immunohistochemistry (IHC), FISH and PCR.
Results: Only 1 patient presented with GI symptoms at diagnosis. Endoscopy: Upper GI: abnormal mucosa in 5 cases (38%); Lower GI: abnormal mucosa in 6 cases (45%): mild colitis in 1, multiple micropolyps in 3, a large polyp and multiple micropolyps in 1 and three large polyps with normal mucosa in 1. As a whole, 9 patients (70%) had upper or lower endoscopic findings.
Pathology: 10 cases (77%) had microscopic infiltration by MCL of the upper GI tract and 10 cases (77%) of the lower GI tract. As a whole, all but one patient (92%) were found to have microscopic infiltration of the GI tract. All positive cases for CD20 and CD5 were positive for cyclin D1. The PCR product showed a clear monoclonal peak in 12 out of 19 samples, giving a sensitivity of 63.5% compared with IHC. FISH was positive in 7 out of 11 samples (sensitivity of 64% compared with IHC). All but one case with endoscopic abnormalities had GI microscopic infiltration by MCL and 67% of cases with normal endoscopy were found to have GI tract infiltration by MCL.
Conclusions: In our series, GI involvement by MCL was detected in almost all patients. All patients with endoscopic abnormalities had infiltration by MCL at the microscopic level. In 2/3 of the patients with normal endoscopy, GI tract involvement could be demonstrated at the microscopic level. IHC with cyclin D1 was more efficient than FISH and PCR as a diagnostic tool in this setting.
Analysis of Prognosis in Follicular Lymphoma According to the FLIPI.
Authors: Hashimoto Chizuko , Kanamori Heiwa , Tomita Naoto , Takabayashi Maki , Yamazaki Etsuko , Ogawa Koji , Hattori Michiko , Fujita Hiroyuki , Fujisawa Shin , Motomura Shigeki , Kodama Fumio , Ishigatsubo Yoshiaki 
Published: October 2019

Abstract
By the new treatment approaches, such as rituximab, anti-CD20 radioimmunotherapy, high-dose therapy, transplantation, the outcome of treatment for follicular lymphoma has been improved. However, there are wide alternatives in a treatment of follicular lymphoma to stemcell transplantation from watchful waiting, and analysis of prognosis is important in choice of a therapy. The international non-Hodgkin’s lymphoma prognostic index (IPI) has been used for follicular lymphoma. Recently, a new method of the follicular lymphoma international prognostic index (FLIPI) is reported and attracts attention. We apply these two prognostic models for newly diagnosed follicular lymphoma, and reviewed its availability. 5 factors were used, The IPI (age>60, EN≥2, LDH>N, PS≥2, CS≥3), and the FLIPI (age>60, Hb<12.0g/dl, LDH>N, CS≥3, nodal sites>4), respectively. Between 1988 and 2001, 107 patients of newly diagnosed follicular lymphoma (grade I-III) were analyzed. Response rate, overall survival (OS), and progression free survival (PFS) were calculated for each prognostic model. Patients characteristics were male/female 49/58, median age 54yr. (range 21–87yr.), and histological grade I, II/III 103/4. The median follow-up of our series was 84 months (range 40–206 months). CR, PR was 60.7%, 31.8%, and response rate was 92.5%. Median OS at 10 years was 64.4%, and median PFS at 10 years was 28.5%. Patient distribution by the IPI and the FLIPI were the followings; the IPI (L/LI/HI/H 49/41/15/2), the FLIPI (L/I/H 41/29/37). There were few patients equivalent to high risk group in IPI, and it was the patient distribution which was more equal in FLIPI in comparison with IPI.
OS by the IPI and the FLIPI risk group at 10 year were L: 85%, LI: 54%, HI: 44%, H: 50% (p=0.0088), and L: 87%, I: 66%, H: 47% (p<0.0001). PFS by the IPI and the FLIPI risk group at 10 year were L: 36%, LI: 23%, HI: 27%, H: 0% (p=0.0679), and L: 43%, I: 25%, H: 16% (p=0.0003). Correlation with a survival was recognized in FLIPI on OS, PFS more by significantly. As a conclusion, the FLIPI is a promising consequence prediction model. A standard treatment for follicular lymphoma is not established, and the examination that a treatment on the basis of prognosticator is strategic is necessary in future. As for grade 3, there was a little number of patients in this study, but further examination is necessary for adaptation of the FLIPI about this group.