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Purpose Nivolumab is an anti-programmed cell death protein 1 (PD1) monoclonal antibody that is indicated in relapsed/refractory Hodgkin lymphoma (R/R HL) after autologous stem cell transplant (autoSCT). Purpose of our retrospective study was to assess safety and efficacy of Nivolumab in R/R HL as a bridge to autoSCT in patients who are refractory to ≥ 2 lines of chemotherapy. Methods Demographic data, number of chemotherapy regimens given previously, number of Nivolumab doses taken, and disease status on PET/CT were noted. Nivolumab was administered as a 3 mg/kg IV infusion every 2 weeks. The immunotherapy related adverse events (irAEs) were noted if any and documented. Results A total of 16 patients were included in the study. Ten patients were male and 6 were female. Median age was 22 years (range 3–32 years). The median number of treatment lines prior to Nivolumab was 3 (range 2–7). Nine patients had Complete Response (CR), 3 had Partial response (PR), 2 had Stable Disease (SD), 1 patient had pseudo-progression; classified as IR (3) and 1 expired before end of treatment evaluation. The drug was well tolerated, with mild irAEs noted. Twelve patients (75%) successfully underwent autoSCT. At a median follow up of 17.5 months (range 0.5–35 months), the progression- free survival (PFS) was 75% and overall survival (OS) was 87.5%. Conclusion Nivolumab is effective and safe in patients with R/R HL and is a good bridging therapy to autoSCT.

Introduction: Birth preparedness is that the process of designing for the birth. Aim this study aimed to assess the birth preparedness knowledge, attitude and practice of primigravida women. Design: A descriptive survey approach adopted to assess the knowledge regarding birth preparedness among primigravida women. Tool: Using 20 items questionnaire was conducted in non probability convenience sampling technique. The Sample setting is chosen hospital in Visnagar. Sample Size: The sample size was 40. Result: the study identified that the 8(20% ) women having good, 27(67.5%) women have average and also the 5(12.5%) women have poor knowledge and birth preparedness among primigravida. Thus study result shows the pre test average is 11.95 and variance is 2.991. &nbsp

Introduction: Hemorrhagic cystitis (HC) is a well-known complication in patients undergoing hematopoeitic stem cell transplantation (HSCT), contributing considerably to morbidity and prolonged hospital stay. Granulocyte-macrophage colony-stimulating factor (GM-CSF) affects the proliferation and differentiation of hematopoietic stem/progenitor cells and the functioning of monocytes, granulocytes, lymphocytes, and endothelial cells. The objective of this study was to evaluate the efficacy and safety of GM-CSF bladder irrigation for HC post-HSCT. Materials and Methods: We conducted a retrospective cohort study to assess the clinical effects of GM-CSF (GM-CSF group) in controlling HC in patients who had undergone HSCT at our institute. We also compared these patients with those who did not receive GM-CSF. Results: There were 12 patients in the GM-CSF group and seven patients in the non-GM-CSF (control) group. The median ages were 16 years (range: 4–33 years) and 19 years (range; 6–41 years), respectively. Median time-to-resolution of HC from day of onset was 9.5 days in the GM-CSF group versus 59 days in the non GM-CSF group (P = 0.001). Mortality was 85% in the control group as compared to 16% in GM-CSF group (P = 0.008). Among the GM-CSF responders, complete response was seen in eight patients (67%). None of the patients developed any systemic or local side effects to GM-CSF. Overall survival in the two groups was 75% and 14%, respectively (P = 0.043). Conclusion: GM-CSF was shown to be effective in controlling HC in post-HSCT patients, without any major side effects, along with decreased mortality and improved overall survival.

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal, acquired hematopoietic stem cell disorder, which is caused by activation of the complement system leading to life-threatening manifestations such as hemolysis, thrombosis, and marrow failure. Eculizumab is a complement inhibitor of C5, which acts by blocking complement-mediated hemolysis. It needs to be administered lifelong to the patient; hence, there are major financial implications. This drug is easily available in the Western countries; however, in low resource countries, where its availability is limited, hematopoietic stem cell transplantation (HSCT) still remains the main modality for achieving cure in PNH. PNH being a rare disease, large prospective studies and guidelines are scarce. To choose the ideal candidate for transplant is the real challenge. This article aims to review the trends in HSCT for PNH, such as the use of reduced-intensity conditioning to attain the graft versus PNH effect or the use of haploidentical donors. In the era of complement inhibitor therapy, the role of transplantation still needs to be explored.

Background: Danon disease (DD) is an X-linked disorder caused by mutations in the LAMP2 gene that is essential for autophagy. DD is characterized by severe cardiomyopathy for which treatment options are limited. Median survival for male patients (pts) is approximately 19 years (y). DD natural history is notable for modest cardiac abnormalities in early phases detectable by measurement of left ventricular global longitudinal strain (GLS) or natriuretic peptides (NPs) followed by rapid progression, particularly in males during the second and third decade. Methods: This open-label Phase 1 study evaluates the safety of a single IV infusion of RP-A501 (AAV9. LAMP2B ) at dose levels of 6.7 x 10 13 GC/kg (low dose) and 1.1 x 10 14 GC/kg (high dose) in male DD pts in two age groups: ≥15 y and 8-14 y. Eligibility criteria include a DD diagnosis with LAMP2 mutation and cardiac involvement. Results: In Cohort 1 (N=3 pts, ≥15 y, 6.7 x 10 13 GC/kg), RP-A501 increased cardiac LAMP2B expression by Western blot (WB) and immunohistochemistry (IHC) in myocardial tissue. The two pts in Cohort 1 with observed immunosuppressive regimen compliance had high cardiac LAMP2B expression: 67.8% and 92.4% vs. normal control by IHC; up to 61% by WB. In both pts, NYHA Class improved from II to I. NPs were reduced by 59% and 42% at 9 and 12 months, respectively. All 3 pts had similar or mildly improved 6MWT, improved myocardial EM morphology with decreased autophagic vacuoles, improved/stabilized GLS and reported increases in physical activity. Adverse events were mostly manageable with transient immunosuppression. Reversible platelet decreases and transaminase elevations that returned to baseline within 2 months were seen. One patient treated with 1.1 x 10 14 GC/kg had complement-mediated thrombocytopenia and acute kidney injury requiring transient hemodialysis that fully recovered. An exacerbation of skeletal myopathy in 3 of the 5 patients resolved with steroid taper. Conclusions: This ongoing first-in-human trial demonstrates that the low dose of RP-A501 gene therapy for DD was generally well-tolerated, confers cardiac LAMP2B gene expression, and is associated with preliminary evidence of cardiac and clinical benefits.

Early mixed chimerism (MC) can lead to secondary graft rejection post allogeneic hematopoietic stem cell transplantation in transfusion dependent thalassemia (TDT) patients. Reduction of immunosuppression and donor lymphocyte infusions is the mainstay for treating MC. We report our experience of administering unmanipulated stem cell boost (SCB) in reversing progressive early MC. There were 70 transplants done for 69 TDT patients at our center between September 2005 and January 2020. Mixed chimerism was defined by > 5% recipient cells and the severity was assigned according to the proportion of recipient cells as level 1 = 25%. For patients developing MC level 2 and 3, we administered unmanipulated SCB and analyzed its safety and efficacy. Out of 70 transplants 7 (10%) had MC level 2 (3/7) and 3 (4/7). These patients received unmanipulated SCB at a median CD34 cell dose of 4.5 × 10(6)/kg (range—3.5 × 10(6)/kg–5.5 × 10(6)/kg). Overall Response (stable MC and/or transfusion independency) to unmanipulated SCB was seen in 5 patients (71.4%). Five patients (71.4%) developed acute graft versus host disease (GVHD) of which 1 patient expired due to severe GVHD. SCB infusion was well tolerated by majority of our patients. The 3 year overall survival and thalassemia free survival was 85.7% (6/7) and 57.1% (4/7) respectively. Timely monitoring of chimerism is important for detecting early MC. Development of acute GVHD is common after administration of unmanipulated SCB and requires vigilance and prompt management. Unmanipulated SCB is a feasible modality for treating progressive MC and salvaging the graft especially in resource-constrained settings.

INTRODUCTION AND OBJECTIVE:Hematuria is associated with 5-10% risk of urothelial malignancy and is the most common symptom in bladder cancer. The American Urological Association (AUA) recommends th...

INTRODUCTION AND OBJECTIVE:Postoperative complications after radical cystectomy are common and bear significant impact to the patient. Over 60% of patients will experience some type of complication...

Background: To present a stepwise description and outcomes of bladder neck sparing (BNS) robot-assisted simple prostatectomy (RASP). Methods: Between March 2015 and December 2018, 30 consecutive patients with benign prostate hyperplasia underwent BNS RASP. Baseline characteristics, and intraoperative and postoperative variables were retrospectively abstracted. Descriptive statistics were used to report the variables. Results: The median age was 66.5 (59.3-72.3) years, and median body mass index was 27.6 (24.5-72.3) kg/m2. The median preoperative International Prostate Symptoms Score was 23 (17.5-27), and median prostate size was 97 (74-148.75) mL. The mean (standard deviation [SD]) operative time was 107.5 (22.2) minutes, and the mean (SD) estimated blood loss was 132.4 (35.4) mL. All cases were completed robotically without any intraoperative complications, and continuous bladder irrigation was not necessary for any patient postoperatively. All patients were able to void after catheter removal except one patient with a preexisting diagnosis of neurogenic bladder who resumed clean intermittent catheterization. All patients were continent as defined as using 0 pads postoperatively. Of the 19 patients who had antegrade ejaculation before the operation, 8 patients (42%) reported of continued antegrade ejaculation after the operation. Conclusions: In this report, we demonstrate a simplified approach of BNS RASP that is reproducible with a favorable perioperative complication rates and acceptable postoperative functional outcomes. This technique obviates the need for continuous bladder irrigation and intraperitoneal drain.

Background: Advanced biliary tract cancer (ABC) has a poor prognosis for which cisplatin-gemcitabine is the reference first-line chemotherapy. No robust evidence is available for second-line chemotherapy. Methods: Patients with ABC who progressed on first-line cisplatin-gemcitabine were randomised to active symptom control (ASC) and oxaliplatin and 5-fluorouracil (FOLFOX) or ASC alone. The primary end-point was overall survival (OS); recruitment of 162 patients was required, to deliver 148 events (hypothesised hazard ratio (HR) 0.63; 80% power; 5% two-sided alpha). Secondary end-points included progression-free survival (PFS) and response rate (ASC+FOLFOX arm only). Results: A total of 162 patients were randomised (81 in each arm) between 27-Mar-2014 and 04-Jan-2018). The median age was 65 years (range 26-84); 80 (49%) were male and the primary tumour sites were intrahepatic cholangiocarcinoma (CCA) 72 (44%), extrahepatic CCA 45 (28%), gallbladder 34 (21%) and ampullary cancer 11 (7%). After 150 OS events, the adjusted HR was 0.69 (95%CI-0.50-0.97; p=0.031; ASC+FOLFOX vs ASC). Median OS (months (m)), 6m and 12m OS-rate (%) were 6.2m, 50.6% and 25.9% for the ASC+FOLFOX and 5.3m, 35.5%, 11.4% for the ASC arm, respectively. The median PFS was 4.0 months (95%-CI 3.2-5.0); the response rate was 5% and the disease control rate 33%. Grade 3-5 adverse events were reported in 56 (69%) and 42 (52%) patients in the ASC+FOLFOX and ASC arm, respectively, including two chemotherapy-related deaths. Conclusion: FOLFOX improved OS after progression to cisplatin-gemcitabine with a clinically-meaningful increase in 6m and 12m OS rate. FOLFOX should become standard-of-care in second-line for ABC. Trial Registration: NCT01926236, EudraCT: 2013-001812-30. Funding Statement: The study was sponsored by The Christie NHS Foundation Trust. The ABC-6 study was funded by Cancer Research UK (CRUK/13/004), StandUpToCancer, AMMF (The UK Cholangiocarcinoma Charity) and The Christie Charity. The Cholangiocarcinoma Foundation provided funding translational research. Dr Angela Lamarca received funding from ESMO (European Society for Medical Oncology), SEOM (Sociedad Espanola de Oncologia Medica) and Conquer Cancer Foundation (Young Investigator Award) fellowship programs and from The Christie Charity. Declaration of Interests: Dr Angela Lamarca received travel and educational support from Ipsen, Pfizer, Bayer, AAA, SirtEx, Novartis, Mylan and Delcath; speaker honoraria from Merck, Pfizer, Ipsen and Incyte; advisory honoraria from EISAI, Nutricia Ipsen, QED and Roche; she is also a member of the Knowledge Network and NETConnect Initiatives funded by Ipsen. Prof Daniel H Palmer declares research grants from AstraZeneca, Bayer, BMS, Nucana, Sirtex; and Consulting or Advisory roles for AstraZeneca, Bayer, BMS, Eisai, MSD, Servier, Roche. Harpreet Singh Wasan declares no conflict of interest associated to this work. Dr Paul J Ross declares research grants from research grants from Sanofi, Bayer; Consulting or Advisory roles for Bayer, BMS, Eisai, Sirtex, Roche; speaker fees from Amgen, Roche, Servier; Travel grants from Bayer, Roche, Servier. Dr Yuk Ting Ma declares speaker honoraria and advisory roles for Bayer, Eisai and Roche. Dr Arvind Arora declares no conflict of interest. Dr Stephen Flak declares no conflict of interest. Dr Roopinder Gilmore declares no conflict of interest. Prof Jon Wadsley declares research grants from AstraZeneca and Sanofi-Genzyme and Consulting or Advisory roles for Lilly, AstraZeneca, Sanofi Genyme, Eisai, AAA, Roche, Novartis, Ipsen. Dr Kinnari Patel declares no conflict of interest. Alan Anthony declares no conflict of interest. Prof Anthony Maraveyas declares research grants from Pfizer, BMS and Bayer. Speaker fees from BMS. Bayer Ipsen, EUSA Pharma, Daiichi Sankyo and Pfizer and advisory roles for Bayer ,BMS, Leo, Pfizer, Merck and Ipsen. Dr Tim Iveson declares no conflict of interest. Dr Justin S Walters received educational support for travel and conference attendance from Mylan and Ipsen, and speaker honoraria from Mylan. Dr Claire Hobbs declares no conflict of interest. Safia Barber declares no conflict of interest. David Ryder declares no conflict of interest. Prof John Ramage declares research grants, speaker fees and advisory roles for Ipsen, Novartis and AAA. Linda M Davies declares no conflict of interest. Prof John Bridgewater declares Consulting or Advisory role for Merck Serono, SERVIER, Roche, Bayer, AstraZeneca, Incyte and Basilea; travel support from MSD oncology, Merck Serono, Servier and BMS. Prof Juan W Valle declares Consulting or Advisory role for Agios, AstraZeneca, Delcath Systems, Keocyt, Genoscience Pharma, Incyte, Ipsen, Merck, Mundipharma EDO, Novartis, PCI Biotech, Pfizer, PierisPharmaceuticals, QED and Wren Laboratories; Speakers’ Bureau for Imaging Equipment Limited Ipsen Novartis Nucana; and Travel Grants from Celgene and Nucana. Ethics Approval Statement: The study was conducted in accordance with the principles of Good Clinical Practice and the Declaration of Helsinki. The study protocol was approved by a research ethics committee and all patients were required to provide written informed consent.

Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) and cyclosporine A (CsA) is the first-line therapy for acquired aplastic anemia (AA) in those not suitable for bone marrow transplant. Horse ATG (hATG) is preferred for this purpose, but its use is often impeded by shortages and costs. Being a rare disease, there is limited data on this therapy. This study aimed to evaluate this therapy in a large cohort of AA patients from western India. We retrospectively analyzed AA patients who received an indigenous preparation of hATG along with CsA as first-line treatment, between 2012 and 2015, at our center and evaluated the response, survival, and occurrence of adverse events. The response was further assessed separately for adults and children. During the period, 91 AA patients (4 non-severe, 57 severe and 30 very severe) were treated with IST. At 2 years, 23.5% adults and 39.1% children showed complete response and an overall of 68.1% cases became transfusion independent. More than half of the patients developed febrile neutropenia while roughly one sixth of the patients developed gum hypertrophy and/or hypertension. Two patients had clonal evolution. Mortality rate was calculated to be 31%; most common causes of death were infection and intracranial hemorrhage. The results of the study substantiate the effectiveness of IST in AA, using an inexpensive indigenous preparation of hATG along with CsA.

Post transplant Hemophagocytic lymphohistiocytosis (HLH) is a form of secondary HLH, which can be either early onset or late onset and is associated with significant morbidity and mortality. With the increasing popularity of post transplant cyclophosphamide based haploidentical stem cell transplantation (SCT), post transplant HLH is becoming a significant complication especially in benign hematological disorders. Methods: We present 4 cases of post transplant HLH occurring in 2 cases of severe aplastic anemia (post haploidentical SCT) and 2 cases of thalassemia major (post matched sibling SCT). All 4 cases had early onset variety with dismal prognosis. Conclusion: Post-transplant HLH is an important entity in benign hematological disorders, which needs to be identified early and treated promptly with steroids, monoclonal agents or immunosuppressive therapy. Serum ferritin levels are an important biomarker and help in monitoring response.

OBJECTIVE To evaluate programmed death ligand 1 (PD-L1) staining fidelity between the primary tumor and associated lymph node metastases in bladder cancer. To secondarily evaluate whether neoadjuvant chemotherapy (NAC) affects this relationship. METHODS Sixty-seven subjects with residual bladder cancer on cystectomy and associated positive lymph nodes were identified between 2008 and 2015. PD-L1 staining of tumor cells was evaluated using H score and 49 specimens were also evaluated using combined positive score (CPS). Univariable and multivariable logistic regression analysis were used to assess how various clinical variables affected odds of PD-L1 fidelity between primary and metastatic tumors. RESULTS Tumor PD-L1 staining was concordant in 79.1% of cases and CPS was concordant in 79.6% of cases. NAC did not significantly impact odds of PD-L1 or CPS fidelity (OR 1.974, 95% CI 0.673-5.784, OR 0.500, 95% CI 0.093-2.700). Among clinical variables analyzed on univariable analysis of tumor PD-L1 fidelity, H-score, and PD-L1 staining intensity were associated with significantly increased odds of PD-L1 fidelity and the association with staining intensity was confirmed on multivariable analysis. CONCLUSION PD-L1 fidelity between primary bladder tumors and nodal metastases was observed in >75% of cases in this study. Additionally, NAC was not shown to diminish this propensity to maintain PD-L1 staining status. Further standardization of immunohistochemistry of tumor and infiltrating imsmune cells in metastatic bladder cancer is needed to improve application of therapeutics.

Importance: Older and/or frail patients are underrepresented in landmark cancer trials. Tailored research is needed to address this evidence gap. Objective: The GO2 randomized clinical trial sought to optimize chemotherapy dosing in older and/or frail patients with advanced gastroesophageal cancer, and explored baseline geriatric assessment (GA) as a tool for treatment decision-making. Design, Setting, and Participants: This multicenter, noninferiority, open-label randomized trial took place at oncology clinics in the United Kingdom with nurse-led geriatric health assessment. Patients were recruited for whom full-dose combination chemotherapy was considered unsuitable because of advanced age and/or frailty. Interventions: There were 2 randomizations that were performed: CHEMO-INTENSITY compared oxaliplatin/capecitabine at Level A (oxaliplatin 130 mg/m 2on day 1, capecitabine 625 mg/m 2twice daily on days 1-21, on a 21-day cycle), Level B (doses 0.8 times A), or Level C (doses 0.6 times A). Alternatively, if the patient and clinician agreed the indication for chemotherapy was uncertain, the patient could instead enter CHEMO-BSC, comparing Level C vs best supportive care. Main Outcomes and Measures: First, broad noninferiority of the lower doses vs reference (Level A) was assessed using a permissive boundary of 34 days reduction in progression-free survival (PFS) (hazard ratio, HR = 1.34), selected as acceptable by a forum of patients and clinicians. Then, the patient experience was compared using Overall Treatment Utility (OTU), which combines efficacy, toxic effects, quality of life, and patient value/acceptability. For CHEMO-BSC, the main outcome measure was overall survival. Results: A total of 514 patients entered CHEMO-INTENSITY, of whom 385 (75%) were men and 299 (58%) were severely frail, with median age 76 years. Noninferior PFS was confirmed for Levels B vs A (HR = 1.09 [95% CI, 0.89-1.32]) and C vs A (HR = 1.10 [95% CI, 0.90-1.33]). Level C produced less toxic effects and better OTU than A or B. No subgroup benefited from higher doses: Level C produced better OTU even in younger or less frail patients. A total of 45 patients entered the CHEMO-BSC randomization: overall survival was nonsignificantly longer with chemotherapy: median 6.1 vs 3.0 months (HR = 0.69 [95% CI, 0.32-1.48], P =.34). In multivariate analysis in 522 patients with all variables available, baseline frailty, quality of life, and neutrophil to lymphocyte ratio were independently associated with OTU, and can be combined in a model to estimate the probability of different outcomes. Conclusions and Relevance: This phase 3 randomized clinical trial found that reduced-intensity chemotherapy provided a better patient experience without significantly compromising cancer control and should be considered for older and/or frail patients. Baseline geriatric assessment can help predict the utility of chemotherapy but did not identify a group benefiting from higher-dose treatment. Trial Registration: isrctn.org Identifier: ISRCTN44687907.

Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL; BCR-ABL1-like ALL) in children with National Cancer Institute (NCI) intermediate- or high-risk (HR) ALL is associated with poor outcome. Ph-like ALL is characterized by genetic alterations that activate cytokine receptor and kinase signaling and may be amenable to treatment with tyrosine kinase inhibitors. The prevalence, outcome, and potential for targeted therapy of Ph-like ALL in standard-risk (SR) ALL is less clear. We retrospectively analyzed a cohort of 1023 SR childhood B-ALL consecutively enrolled in the Children's Oncology Group AALL0331 clinical trial. The Ph-like ALL gene expression profile was identified in 206 patients, and 67 patients with either BCR-ABL1 (n = 6) or ETV6-RUNX1 (n = 61) were excluded from downstream analysis, leaving 139 of 1023 (13.6%) as Ph-like. Targeted reverse transcription polymerase chain reaction assays and RNA-sequencing identified kinase-activating alterations in 38.8% of SR Ph-like cases, including CRLF2 rearrangements (29.5% of Ph-like), ABL-class fusions (1.4%), JAK2 fusions (1.4%), an NTRK3 fusion (0.7%), and other sequence mutations (IL7R, KRAS, NRAS; 5.6%). Patients with Ph-like ALL had inferior 7-year event-free survival compared with non-Ph-like ALL (82.4 ± 3.6% vs 90.7 ± 1.0%, P = .0022), with no difference in overall survival (93.2 ± 2.4% vs 95.8 ± 0.7%, P = .14). These findings illustrate the significant differences in the spectrum of kinase alterations and clinical outcome of Ph-like ALL based on presenting clinical features and establish that genomic alterations potentially targetable with approved kinase inhibitors are less frequent in SR than in HR ALL.

Stream data mining is the process of excerpting knowledge structure from large, continuous data. For stream data, various techniques are proposed for preparing the data for data mining task. In recent years stream data have become a growing area for the researcher, but there are many issues occurring in classifying these data due to erroneous and noisy data. Change of trend in the data periodically produces major challenge for data miners. This research concentrates on incremental missing value replacement for stream data. The proposed method generates the value for the missing data considering the data type and data distribution. It also considers the concept drift in the data stream. The method is applied to different datasets and promising results derived.

Background Hematopoietic stem cell transplantation (HSCT) is challenging in Hbs-Ag positive or HCV-Ab positive patients due to fear of delaying engraftment and transplant-related mortality (TRM). Very few data are published internationally till date. We had done HSCT (allogenic/autologus) of 19 hepatitis B and hepatitis C positive malignant and nonmalignant patients at our institute during the years 1999–2013. Design and methods We performed a retrospective analysis of the patients who were either hepatitis B or hepatitis C virus seropositive at the time of HSCT ( n = 19). All the positive patients (Hbs-Ag positive or HCV-Ab positive) who underwent HSCT for malignant or nonmalignant causes during 1999–2013 were selected. A total of 13 patients underwent autologus HSCT and 6 patients underwent allogenic HSCT. All the included patients had performance score 1, normal liver function test, and noninfectious state of Hbe antigen before HSCT. Results The median age of the seropositive patients was 25 years (range 7–54); 16 patients were Hbs-Ag positive and 3 were HCV-Ab positive. Most common indication of HSCT was lymphoma ( n = 12), in which 7 patients were of Hodgkin disease and 5 patients were of non-Hodgkin disease (NHL). Three patients were acute myeloid leukemia, 2 patients of thalassemia major, 1 patient was of chronic myeloid leukemia-chronic phase, and 1 of multiple myeloma. We had used high-dose chemotherapy for induction with carmustine, etoposide, cytarabine, and melphalan (BEAM) for autologus HSCT and busulfan, cyclophosphamide (BUCY), busulfan, cyclophosphamide-thymoglobulin (BUCY-THYMO), and reduced intensity HSCT (RIST) for allogenic HSCT. All the patients underwent successful engraftment except one NHL patient. The median duration of neutropenia was 14 and 11 days in the allogenic HSCT and autologus HSCT, respectively. Median duration for engraftment of neutrophils was achieved on +Day 17 with 3 consecutive absolute neutrophil counts of more than 500 cumm/dL. Median duration for engraftment of platelets was achieved on +Day 19 with 3 consecutive platelet counts of more than 50,000 cumm/dL without any component support. Out of 6 allogenic HSCT patients, 4 developed graft versus host disease (GVHD) (2 – liver, 1 – colon, 1 – both skin and liver). Three patients died due to liver GVHD (2 – acute, 1 – chronic). Grades of GVHD in allogeneic HSCT patients are as follows, for liver (grade 3 in 2, grade 4 in 1), colon (grade 2 in 1), and skin (grade 2 in 1). Out of the 8 patients, one patient developed grade 3 veno-occlusive disease. Median at 100 days, 1-year overall survival (OS), and 5-year OS were 89.4%, 94.1%, and 81.1%, respectively. Conclusions HSCT is a rugged job in Hbs-Ag positive or HCV-Ab positive patients due to more complications in the form of more neutropenia, GVHD, drug toxicity of chemotherapy, acute fulminant liver failure, fear of delaying of engraftment, and TRM. Careful evaluation before embarking on HSCT and intensive assessment against complications are warranted in Hbs-Ag positive and HCV-Ab positive recipients.

Objective To evaluate active surveillance (AS) criteria on their ability to predict favorable pathology at prostatectomy within a low-risk African American (AA) cohort. Methods The sensitivity, specificity, positive predictive value, receiver operator curve, and area under the curve (AUC) were compared for 6 published AS criteria (National Comprehensive Cancer Network; Memorial Sloan-Kettering Cancer Center; Prostate Cancer Research International: Active Surveillance Study; Johns Hopkins–Epstein; University of California at San Francisco; and University of Miami) to predict organ-confined Gleason score 6 disease at prostatectomy in AAs and white Americans (WAs) with low-risk cancer. We also compared clinical parameters for AAs with favorable prostatectomy pathology with those for AAs with unfavorable pathology, and then used preoperative variables associated with unfavorable pathology as an additional exclusion criteria for AS. Results Of 468 patients with low-risk disease, 308 of 402 (76.6%) WAs and 55 of 66 (83.3%) AAs were eligible for AS by one or more criteria (P = .23). For WAs, Prostate Cancer Research International: Active Surveillance Study criteria had the highest rate of favorable pathology (81.7%) and the best performance (AUC = 0.70) in determining appropriate candidates for AS. However, all 6 AS criteria performed poorly for AA patients, with all AUCs ≤0.52. When comparing AAs with favorable pathology with AAs with unfavorable pathology, only family history of prostate cancer was statistically significant (11 of 25 [47.8%] vs 8 of 41 [22.2%]; P = .04). When adjusting AS criteria in AAs to exclude those with a positive family history, the AUC increased most for the University of California at San Francisco (from 0.52 to 0.6) and Memorial Sloan-Kettering Cancer Center criteria (from 0.50 to 0.58). Conclusion Current criteria underperform in appropriately selecting AAs for AS. AAs considering AS should be counseled about their increased risk for occult adverse pathology, particularly if a family history of prostate cancer is present.

Beta thalassemia major, one of the most prevalent hemoglobinopathy throughout the word, can be cured by allogenic stem cell transplantation (SCT) (Bone Marrow Transplant 36:971-975, 2005). Many patients, however, lack a suitably matched related sibling donor. Unrelated umbilical cord blood (UCB) can be used as an alternative stem cell source for these patients. This report describes SCT for nine children with beta-thalassemia major using partially HLA-matched unrelated UCB. Conditioning included oral busulfan 16 mg/kg (day -10 to -7), cyclophosphamide (Cy) 200 mg/kg (day -5 to -2), fludarabine 90 mg/kg (day -13 to -11), and antithymocyte globulin (rabbit) 7.5 mg/kg (day -3 to -1). The infused cell dose was 10.71 × 10(7)/kg total nucleated cells (TNC) (range 6.5-17 × 10(7)/kg TNC). The patients ranged in age from 1.5 to 7 years, in weight from 10.5 to 17 kg. A second transplant with two unrelated cord blood units was attempted in two patients who had primary graft failure. The retransplant recipients were preconditioned with i.v Cy 120 mg/kg (day -3 to -2). Five of the nine patients engrafted promptly with 50-100 % donor chimerism (56 %). They engrafted at a median of 17 days (range 12-19). One patient is transfusion free for 36 months; a second patient is transfusion free for 18 months and a third is transfusion free for 9 months. There was no transplant related mortality. Four of the nine children had autologous recovery without engraftment. Primary graft rejection is the major complication. Post transplant complications were mild hepatic veno-occlusive disease, acute GVHD grade II, and CMV interstitial pneumonia. The chronic GVHD was limited and could be controlled by Methylprednisolone combined with Mycophenolate. The lack of a marrow donor registry in India makes UCBT from related and unrelated donors a good alternative. Transplant should be delayed until the child is at least 18 months of age. The dose of UCB stem cells is the most important factor for engraftment. UCB has the advantages of rapid availability and low risk of severe GVHD despite donor-recipient HLA disparity (Transplant Proc 37:2667-2669, 2005). We demonstrate the feasibility of this procedure in the setting of a developing country.

4003 Background: Level A evidence supports use of CisGem as first-line chemotherapy for ABC; no robust evidence is available for second-line chemotherapy. Methods: Pts diagnosed with ABC with disease progression after prior CisGem were randomised (1:1) to either ASC+mFOLFOX or ASC. Randomisation was stratified by serum albumin levels ( < 35 vs ≥35 g/L), platinum sensitivity (determined from first-line CisGem) and disease extent (locally advanced vs metastatic). Pts with ECOG PS0-1, adequate haematological, renal and liver function, and adequate biliary drainage were eligible. Primary end-point was overall survival (OS) (multivariable Cox regression adjusted for stratification factors); sample size: 162 pts delivering 148 events were required (80% power; 5% two-sided alpha) for a hypothesised hazard ratio (HR) of 0.63. Assumed median survival for ASC was 4 months. Results: 162 pts (81 in each arm) were randomised (27 March ‘14 - 04 Jan ‘18); median age 65 yrs (range 26-84); sex: 80 (49%) male, 82 (51%) female; primary site: intrahepatic 72 (44%), extrahepatic 45 (28%), gallbladder 34 (21%) and ampullary 11 (7%). Baseline characteristics were balanced between arms except platinum sensitivity (ASC+mFOLFOX 27 pts (33%); ASC 34 pts (42%)). After 150 OS events, the adjusted HR was 0.69 (95% CI 0.50-0.97; p = 0.031; ASC+mFOLFOX vs ASC). Median OS (months (m)), 6m and 12m OS-rate (%) were 6.2m, 50.6% and 25.9% for the ASC+mFOLFOX and 5.3m, 35.5%, 11.4% for the ASC arm, respectively. Grade 3/4 toxicities were reported in 48 (59%) and 32 (39%) pts in the ASC+mFOLFOX and ASC arm, respectively; these were balanced between arms except for fatigue and neutropenia (more frequent in ASC+mFOLFOX arm); data cleaning is ongoing. No chemotherapy-related deaths were reported. Conclusion: Survival with ASC was greater than assumed; ASC+mFOLFOX improved OS after progression to CisGem with a clinically meaningful increase in 6m and 12m OS rate. ASC+mFOLFOX should become standard of care in second-line for ABC. Clinical trial information: NCT01926236.

Aims: \ud Sorafenib is the current standard treatment for advanced hepatocellular carcinoma. We carried out a national audit of UK patients treated with sorafenib as standard-of-care and those treated with systemic therapy in first-line trials.\ud \ud Materials and methods: \ud Sorafenib-treated and trial-treated patients were identified via the Cancer Drugs Fund and local databases. Data were collected retrospectively from medical records according to a standard case report form. The primary outcome measure was overall survival, estimated by the Kaplan–Meier method.\ud \ud Results: \ud Data were obtained for 448 sorafenib-treated patients from 15 hospitals. The median age was 68 years (range 17–89) and 75% had performance status ≤ 1. At baseline, 77% were Child-Pugh A and 16.1% Child-Pugh B; 38% were albumin–bilirubin grade 1 (ALBI-1) and 48% ALBI-2; 23% were Barcelona Clinic Liver Classification B (BCLC-B) and 72% BCLC-C. The median time on sorafenib was 3.6 months, with a mean daily dose of 590 mg. The median overall survival for 448 evaluable sorafenib-treated patients was 8.5 months. There were significant differences in overall survival comparing Child-Pugh A versus Child-Pugh B (9.5 versus 4.6 months), ALBI-1 versus ALBI-2 (12.9 versus 5.9 months) and BCLC-B versus BCLC-C (13.0 versus 8.3 months). For trial-treated patients (n = 109), the median overall survival was 8.1 months and this was not significantly different from the sorafenib-treated patients.\ud \ud Conclusion: \ud For Child-Pugh A patients with good performance status, survival outcomes were similar to those reported in global randomised controlled trials. Patients with ALBI grade > 1, Child-Pugh B or poor performance status seem to derive limited benefit from sorafenib treatment.

Summary Background The ESPAC-3 trial showed that adjuvant gemcitabine is the standard of care based on similar survival to and less toxicity than adjuvant 5-fluorouracil/folinic acid in patients with resected pancreatic cancer. Other clinical trials have shown better survival and tumour response with gemcitabine and capecitabine than with gemcitabine alone in advanced or metastatic pancreatic cancer. We aimed to determine the efficacy and safety of gemcitabine and capecitabine compared with gemcitabine monotherapy for resected pancreatic cancer. Methods We did a phase 3, two-group, open-label, multicentre, randomised clinical trial at 92 hospitals in England, Scotland, Wales, Germany, France, and Sweden. Eligible patients were aged 18 years or older and had undergone complete macroscopic resection for ductal adenocarcinoma of the pancreas (R0 or R1 resection). We randomly assigned patients (1:1) within 12 weeks of surgery to receive six cycles of either 1000 mg/m 2 gemcitabine alone administered once a week for three of every 4 weeks (one cycle) or with 1660 mg/m 2 oral capecitabine administered for 21 days followed by 7 days' rest (one cycle). Randomisation was based on a minimisation routine, and country was used as a stratification factor. The primary endpoint was overall survival, measured as the time from randomisation until death from any cause, and assessed in the intention-to-treat population. Toxicity was analysed in all patients who received trial treatment. This trial was registered with the EudraCT, number 2007-004299-38, and ISRCTN, number ISRCTN96397434. Findings Of 732 patients enrolled, 730 were included in the final analysis. Of these, 366 were randomly assigned to receive gemcitabine and 364 to gemcitabine plus capecitabine. The Independent Data and Safety Monitoring Committee requested reporting of the results after there were 458 (95%) of a target of 480 deaths. The median overall survival for patients in the gemcitabine plus capecitabine group was 28·0 months (95% CI 23·5–31·5) compared with 25·5 months (22·7–27·9) in the gemcitabine group (hazard ratio 0·82 [95% CI 0·68–0·98], p=0·032). 608 grade 3–4 adverse events were reported by 226 of 359 patients in the gemcitabine plus capecitabine group compared with 481 grade 3–4 adverse events in 196 of 366 patients in the gemcitabine group. Interpretation The adjuvant combination of gemcitabine and capecitabine should be the new standard of care following resection for pancreatic ductal adenocarcinoma. Funding Cancer Research UK.

International audience; BACKGROUND & AIMS: The Albumin-Bilirubin (ALBI) grade was proposed as an objective means to evaluate liver function in patients with Hepatocellular Carcinoma (HCC). ALBI grade 1 vs 2 were proposed as stratification factors within the Child Pugh (CP) A class. However, the original publication did not provide comparison with the subclassification by points (5-15) within the CP classification. METHODS: We retrospectively analysed data from patients treated with sorafenib for HCC from 17 centres in United Kingdom and France. Overall survival (OS) was analysed using the Kaplan-Meier method and a Cox regression model. Discriminatory abilities of the classifications were assessed with the log likelihood ratio, Harrell's C statistics and Akaike information criterion. RESULTS: Data from 1019 patients were collected, of which 905 could be assessed for both scores. 92% of ALBI grade 1 were CP A5 while ALBI 2 included a broad range of CP scores of which 44% were CP A6. Median OS was 10.2, 7.0 and 3.6 months for CP scores A5, A6 and >A6, respectively (P < 0.001), Hazard Ratio (HR) = 1.60 (95%CI: 1.35-1.89, P < 0.001) for A6 vs A5. Median OS was 10.9, 6.6 and 3.0 months for ALBI grade 1, 2 and 3, respectively (P < 0.001), HR = 1.68 (1.43-1.97, P < 0.001) for grade 2 vs 1. Discriminatory abilities of CP and ALBI were similar in the CP A population, but better for CP in the overall population. CONCLUSIONS: Our findings support the use CP class A as an inclusion criterion, and ALBI as a stratification factor in trials of systemic therapy.

In this paper, we present a model that can be used to determine semiconductor material parameters for metal-semiconductor contacts with non-linear voltage-current (V-I) characteristics. The model uses the Circular Transmission Line Model (CTLM) approach to calculate sheet resistance (RSH) and resistivity (ρ) of Mg doped HVPE and MBE GaN epilayers giving values close to those achieved by Hall measurements.

In this work we report on the magnetron reactive ion etch (MRIE) technology for gallium nitride (GaN) and aluminum gallium nitride (Al x Ga1−x N) using dichlorodifluoromethane (CCl2F2), commonly known as halocarbon 12, with etch rates greater than 1,000 and 840 A/min, respectively. Magnetic confinement of a very low pressure (10−4 Torr range) radio frequency (RF) discharge generates high-density plasmas, with low sheath voltages at the bounding surfaces, and very high dissociation of the source gas. Furthermore, the very low pressure of the etch process is characterized by long mean free paths so that sputtering contamination is reduced. MRIE chemistry has been monitored in situ by means of mass spectroscopy. Finally, we report on the successful fabrication of an indium gallium nitride (In x Ga1−x N) blue light emitting diode (LED), whose fabrication sequence included the MRIE etching of GaN in CCl2F2.

We report analysis of all consecutive Hodgkins disease patients undergoing autologous hematopoietic stem cell transplant from September 1999 to December 2014. Out of total 38 patients 26 were males and 12 were females. 32 were adults and 6 were pediatric (

Total 26 children of thalassemia underwent hematopoetic stem cell transplantation from September 2006 to December 2014. Out of these 17 were matched sibling transplantation (MST) and 9 were unrelated umbilical cord blood transplantation (UCT). Median age was 4 years. At a median follow up of 46.5 months, 12 of 17 (70 %) MST and 3 out of 9 (33.33 %) UCT were cured of thalassemia. Three (11.53 %) patients died due to transplant related mortality. Average cost of MST was 6 lakhs and that of UCT was 20 lakhs.

The most frequent form of congenital dyserythropoiesis (CDA) is congenital dyserythropoietic anemia II (CDA II). CDA II is a rare genetic anemia in humans, inherited in an autosomally recessive mode, characterized by hepatosplenomegaly normocytic anemia and hemolytic jaundice. Patients are usually transfusion-independent except in severe type. We are here reporting a case of severe transfusion-dependent type II congenital dyserythropoietic anemia in a 5-year-old patient who has undergone allogeneic hematopoietic stem cell transplantation (HSCT) at our bone marrow transplantation centre. Patient has had up until now more than 14 mL/kg/month of packed cell volume (PCV), which he required every 15 to 20 days to maintain his hemoglobin of 10 gm/dL and hematocrit of 30%. His pre-HSCT serum ferritin was 1500 ng/mL and he was on iron chelating therapy. Donor was HLA identical sibling (younger brother). The preparative regimen used was busulfan, cyclophosphamide, and antithymocyte globulin (Thymoglobulin). Cyclosporine and short-term methotrexate were used for graft versus host disease (GVHD) prophylaxis. Engraftment of donor cells was quick and the posttransplant course was uneventful. The patient is presently alive and doing well and he has been transfusion-independent for the past 33 months after HSCT.

In this work we present preliminary results of MOCVD grown n- GaN and MBE grown p-GaN p-n junctions on a sapphire substrate, with and without II-IV active layers. Circular transmission line method (CTLM) test structures were used to measure sheet resistance, contact resistance and to calculate resistivity of the p-GaN layer in both cases. Atomic force microscopy (AFM) was deployed to characterize the surface morphology of the p-type GaN. LED structures fabricated using standard methods were tested for IV characteristics and electroluminescence was demonstrated

Light emitting diodes (LEDs) with colloidal grown quantum dot active layers may serve as a solution to the efficiency gap in the deep green LED emission spectrum. CdSe quantum dots can be tuned for emission across the visible spectrum including the deep green. This work focuses on integrating a CdSe active layer into a GaN LED.

The objective of our current work is to observe the effects of MBE p-GaN growth over II-VI semiconductor nanocrystals on an MOCVD n-GaN template. The starting material was approximately 2 microns of n-type GaN MOCVD material atop a sapphire wafer. CdSe quantum dots were applied through drop and spin casting. A p-type MBE GaN layer of 2500 A was grown using a nitrogen plasma source. MBE allowed precise growth while SIMS analysis showed the relatively low temperature associated with this method, versus MOCVD, preserved the quantum dots. The surface was investigated using atomic force microscopy in tapping mode for samples at various high/low substrate and magnesium cell temperatures.

In this paper the preliminary results of incorporating a novel active layer into a GaN light emitting diode (LED) are discussed. Integration of colloidal CdSe quantum dots into a GaN LED active layer is demonstrated. Properties of p-type Mg doped overgrowth GaN are examined via circular transmission line method (CTLM). Effects on surface roughness due to the active layer incorporation are examined using atomic force microscopy (AFM). Electroluminescence of LED test structures is reported, and an ideality factor of n = 1.6 is demonstrated.

Given a graph G, the normalized Laplacian associated with the graph G, denoted ${\cal L}$(G), was introduced by F. R. K. Chung and has been intensively studied in the last 10 years. For a k-regular graph G, the normalized Laplacian ${\cal L}$ (G) and the standard Laplacian matrix L(G) satisfy L(G) = k {\cal L} (G), and hence they have the same eigenvectors and their eigenvalues are directly related. However, for an irregular graph G, ${\cal L} (G) and L(G) behave quite differently, and the normalized Laplacian seems to be more natural. In this paper, Cauchy interlacing-type properties of the normalized Laplacian are investigated, and the following result is established. Let G be a graph, and let H = G - e, where e is an edge of G. Let $\lambda_1\geq \lambda_2 \geq \cdots \geq \lambda_{n}=0$ be the eigenvalues of ${\cal L}(G)$, and let $\theta_1\geq \theta_2 \geq \cdots \geq \theta_{n}$ be the eigenvalues of ${\cal L}(H)$. Then, $\lambda_{k-1} \geq \theta_{k}\geq \lambda_{k+1}$ for each k = 1, 2, 3, \dots, n, where $\lambda_{0} =2$ and $\lambda_{n+1}=0$. Applications are given for eigenvalues of graphs obtained from special graphs by adding or deleting a few edges. A short proof is given of the result that $G$ is a graph with each component a nontrivial bipartite graph if and only if $2-\lambda$ is an eigenvalue of ${\cal L}(G)$ for each eigenvalue $\lambda$ of ${\cal L }(G)$.

Twelve adult patients (median age 29.5 years) were started on Eltrombopag 25–50 mg/day for post-hematopoietic stem cell transplantation (HSCT) thrombocytopenia. All patients were having primary thrombocytopenia after HSCT. No patient had other secondary cause for thrombocytopenia. Two patients were allogenic subsets (1 acute myeloid leukemia i.e., AML and 1 aplastic anemia), and 10 were autologous transplants (3 multiple myeloma, 6 lymphoma and 1 AML). Nine patients were males, three were females. The median time of starting Eltrombopag was 21 days post-stem cell infusion (range day +17 to +60) at a median platelet count of 9,000/cmm (range 3,000–11,000/cmm). The median duration for treatment was 29 days. Median total dose of 812.5 mg was received by patients and they had a median platelet increment of 36,000/cmm. We observed that there were no adverse effects in these patients and there was a gradual increase in platelet count so that none of the patients had any complication due to thrombocytopenia. The cost of treatment was less than the cost of extended hospitalization and irradiated single donor platelet transfusion.

Fifteen patients, with a median age of 19 years having severe aplastic anaemia (SAA) underwent human leucocyte antigen (HLA) identical sibling donor hematopoietic stem cell transplantation (HSCT) using conditioning regimens containing cyclophosphamide with antithymocyte globulin (ATG) or a combination of fludarabine and cyclophosphamide with or without ATG during December 2007 to May 2013. Cyclosporine and mini methotrexate were used as graft versus host disease (GVHD) prophylaxis. Graft source included peripheral blood stem cells in 11, bone marrow in 3 and both in 1. One patient had primary graft failure while 14 patients were engrafted with a median neutrophil and platelet engraftment time of 13.5 days. One patient had secondary graft rejection. Acute GVHD occurred in 3 patients and chronic GVHD in 4. One year death rate in engrafted patients was 14.28 %. At a mean follow-up of 21.2 months, 12 (80 %) are alive and well. One of the donors was a patient of haemophilia but the disease did not occur in the recipient. The graft was successful and the recipient is alive till date.