LB6. EDP-938, a Novel RSV N-Inhibitor, Administered Once or Twice Daily Was Safe and Demonstrated Robust Antiviral and Clinical Efficacy in a Healthy Volunteer Challenge Study

Abstract Background Respiratory syncytial virus (RSV) represents an important global health challenge with significant morbidity and mortality in infants, elderly, and immunocompromised adults. No effective therapy is currently available. EDP-938 demonstrates potent in vitro activity against RSV Subtypes A and B. We report data from EDP 938-101, a double-blind, placebo-controlled, Phase 2a study that evaluated EDP-938 in adult volunteers inoculated with RSV-A Memphis 37b. Methods Subjects were healthy volunteers, 18–45 years, who were sero-suitable (i.e., lower 25th percentile). After RSV inoculation on Study Day 0, subjects had 12 hourly nasal wash monitored for RSV infection by qualitative RSV RT–PCR. On Study Day 5 or previously if qualitative RT–PCR was RSV+, subjects were randomized to receive 5 days of EDP-938 600 mg once daily (QD arm) or 500 mg loading dose then 300 mg twice daily (BID arm), or placebo twice daily. Assessments included 12 hourly nasal wash for quantitative RSV viral load, 8 hourly RSV Total Symptom Scoring (TSS) and daily mucus weights. Safety assessments were continued though Day 28 (last follow-up). The primary endpoint was the RSV viral load area under the curve (AUC) from first dose through Day 12 among RSV-infected subjects, defined as the Intent To Treat-Infected (ITT-I) population. The study was fully powered for both RSV viral load and TSS endpoints. Results A total of 115 subjects were randomized and inoculated; 86 were included in the ITT-I analysis. The primary and secondary efficacy endpoints were achieved with high statistical significance in QD and BID arms (figure and table). Among EDP-938 recipients all adverse events (AEs) were mild except for a single AE of moderate dyspepsia in the BID arm and events of moderate headache (n = 2) and hypoacusis (n = 1) in the placebo arm. All AEs resolved in follow-up. Conclusions In the RSV Challenge study, EDP-938 administered once or twice daily achieved primary and key secondary endpoints with robust reductions in RSV viral load (by both qRT–PCR and plaque assays), symptom scores and mucus weights. These data support the further clinical evaluation of EDP-938 in populations at risk of severe RSV disease. Disclosures Eoin Coakley, MD, Enanta Pharmaceuticals (Employee), Alaa Ahmad, PhD, Enanta Pharmaceuticals (Employee), Kajal Larson, PhD, Enanta Pharmaceuticals (Employee), Ty McClure, PhD, Enanta Pharmaceuticals (Employee), Kai Lin, PhD, Enanta Pharmaceuticals (Employee), Kursten Tenhoor, n/a, Enanta Pharmaceuticals (Consultant), Kingsley Eze, n/a, hVIVO Services Ltd. (Employee), Nicolas Noulin, PhD, No financial relationships or conflicts of interest, Veronika Horvathova, MBChB, MSc, hVIVO Services Limited (Other Financial or Material Support, Employed by hVIVO during the conduct of the study), Bryan Murray, MBBS, No financial relationships or conflicts of interest, Mark Baillet, PhD, S-CUBED (Employee), Julie Mori, PhD, hVIVO (Employee, Shareholder) Nathalie Adda, MD, Enanta Pharmaceuticals (Employee).

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Ivermectin in mild and moderate COVID-19 (RIVET-COV): a randomized, placebo-controlled trial

10.21203/rs.3.rs-191648/v1 ◽

2021 ◽

Author(s):

Anant Mohan ◽

Pawan Tiwari ◽

Tejas Suri ◽

Saurabh Mittal ◽

Ankit Patel ◽

...

Keyword(s):

Viral Load ◽

Adverse Events ◽

Controlled Trial ◽

Statistical Significance ◽

Severe Disease ◽

Rt Pcr ◽

Serious Adverse Events ◽

Double Blind ◽

Intention To Treat ◽

Treat Population

Abstract Introduction: Till date, no drug has shown definite benefit in non-severe COVID-19. Ivermectin is an antiparasitic drug which has in-vitro efficacy in reducing coronavirus-2 (SARS-CoV-2) load in severe disease. Objectives: To determine if a single oral administration of Ivermectin to patients with mild and moderate COVID-19 is effective in converting SARS-CoV-2 RT-PCR to negative result and in reducing viral load.Methods: In this double-blind trial, patients were randomized to elixir formulation of Ivermectin in 24 mg, 12 mg or placebo in 1:1:1 ratio. The co-primary outcomes were conversion of RT-PCR to negative result and the decline of viral load at day 5 of enrolment and were assessed in patients with positive RT-PCR at enrolment (modified intention-to-treat population). Safety outcomes included total and serious adverse events and were assessed in all patients who received the trial drug (intention-to-treat population). Results: Among 157 patients randomized, 125 patients were included in mITT analysis. Forty patients each were assigned to Ivermectin 24 mg and 12 mg, and 45 patients to placebo. The RT-PCR negativity at day 5 was higher in the two Ivermectin arms but failed to attain statistical significance (Ivermectin 24 mg, 47.5%; 12 mg, 35.0%; and placebo, 31.1%; p= 0.30). The decline of viral load at day 5 was similar in the three arms. No serious adverse events were encountered.Conclusion: In patients with mild and moderate COVID-19, a single administration of Ivermectin elixir (either 24 mg or 12 mg) demonstrated a trend towards higher proportion of RT-PCR negativity at day 5 of enrolment. The protocol was registered in the Clinical Trial Registry – India (CTRI) vide ref No CTRI/2020/06/026001.

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Developmental Outcomes of Offspring of Adults Treated with Hydroxyurea in the Multicenter Study of Hydroxyurea.

Blood ◽

10.1182/blood.v114.22.1543.1543 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1543-1543 ◽

Cited By ~ 1

Author(s):

F. Daniel Armstrong ◽

Martin H Steinberg ◽

Samir K. Ballas ◽

Kenneth I. Ataga ◽

Myron A Waclawiw ◽

...

Keyword(s):

Adaptive Behavior ◽

Multicenter Study ◽

Drug Exposure ◽

Conflicts Of Interest ◽

Cognitive Outcome ◽

Phase Iii ◽

Vineland Adaptive Behavior Scales ◽

Double Blind ◽

The Average Range

Abstract Abstract 1543 Poster Board I-566 Between 1992-1995, the National Heart, Lung, and Blood Institute sponsored a multi-center, double blind, randomized, placebo-controlled Phase III clinical trial of hydroxyurea (Multicenter Study of Hydroxyurea-MSH). This trial examined whether hydroxyurea, a myelosuppressive chemotherapeutic agent that also stimulates the production of fetal hemoglobin (HbF), would reduce pain episodes in adults with sickle cell anemia. The trial was stopped early because of significant benefits of pain reduction that was sustained in a nine-year follow-up. This also suggested that patients taking hydroxyurea had improved survival. Despite our best attempts to promote contraception among MSH patients, women had children and men fathered children. One of the concerns about using hydroxyurea was that it might have teratogenic effects on offspring, particularly in the area of brain development and cognitive outcome. To address this question, all eligible adults in the MSH trial were contacted to provide consent to obtain developmental outcome data using telephone interview administration of the Vineland Adaptive Behavior Scales, 2nd Edition, Survey Form (VABS). The population mean for the VABS is 100 with a standard deviation of 15. Interviews were conducted by a trained psychologist using an interactive question and answer process, with probes to clarify any information that was unclear. Consent was obtained for parents of 22 offspring meeting criteria for inclusion. A number of the parents had multiple offspring; eight of the study parents were male and three were female. The children ranged from 6-months to 17 years of age at the time of the VABS interview. Four of the parents could not be reached for the interview. Of the remaining 18, four were ineligible because the birth occurred before hydroxyurea was started. As a group, the offspring were functioning in the average range of development in all areas: Adaptive Behavior Composite (M=102.3), Communication Domain (M=98.5), Daily Living Domain (M=103.8), Socialization Domain (M=100.2), and Motor Domain (for children under age 5; M=108.3). One child was functioning below the average range; follow-up determined that this child was in a special education program but had a developmental disability that had occurred in other family members. The number of children who met criteria for this study and whose parents could be contacted was very small, severely limiting any definitive conclusions about developmental risk for offspring. Studies of teratogenicity for prenatal substance abuse have used standardized observational tests of neurodevelopment; this study relied on parent report, which can be biased if not confirmed. When standardized tests have been used in studies of prenatal drug exposure (not hydroxyurea), subtle difficulties in executive function of offspring have been reported, sometimes years after the exposure. While our results are encouraging in that the offspring in this limited group are functioning in the average range, this observation is not conclusive and there is a need to study a larger sample of children who are offspring of adults treated with hydroxyurea according to community standards. Disclosures No relevant conflicts of interest to declare.

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PET -CT Adapted Therapy After 3 Cycles of ABVD for All Stages of Hodgkin Lymphoma. Preliminary Results in 193 Patients

Blood ◽

10.1182/blood.v118.21.1619.1619 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1619-1619 ◽

Cited By ~ 1

Author(s):

Astrid Pavlovsky ◽

Isolda Fernandez ◽

Virginia Prates ◽

Miguel A Pavlovsky ◽

Lucia Zoppegno ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Progressive Disease ◽

Conflicts Of Interest ◽

Statistical Significance ◽

Cell Transplant ◽

Bulky Disease ◽

Radio Therapy ◽

Anatomic Reduction ◽

Pet Ct

Abstract Abstract 1619 Background: Positron emission tomography using 18F-fluoro-2-deoxy-d-glucose (FDG-PET-CT) is an important tool for treatment response assessment in Hodgkin Lymphoma (HL) treated with ABVD. It can predict response and overall outcome. The negative predictive value for PET-CT in patients (pts.) with HL is 90–94%. New recommendations define complete remission (CR) for HL as the lack of signs and symptoms of lymphoma with a negative PET-CT. OBJECTIVES: Reduce therapy in pts. who achieve early CR with negative PET-CT. Intensify treatment, only in pts. with positive PET-CT after 3 cycles of ABVD. Achieve CR, event free survival (EFS) and overall survival (OS), as good as in our historical control, when we used 3 or 6 cycles of ABVD plus involved field radio therapy (IFRT) in all pts.(LH-96) PATIENTS AND METHOD: Since October 2005, 200 newly diagnosed pts. with HL have been included in a prospective multicenter clinical trial (LH-05) All pts. received 3 cycles of ABVD and were then evaluated with a PET-CT (PET-CT +3) Pts. with a negative PET-CT+3 and absence of other signs or symptoms of lymphoma were considered in CR and received no further therapy. Pts with more than 50% of anatomic reduction of initial masses but persistent hyper metabolic lesions were considered in partial response (PR) and completed 6 cycles of ABVD and IFRT on PET-CT positive areas. Pts with less than PR received high doses of chemotherapy and an autologous stem cell transplant (ASCT). All pts were re-evaluated at the end of treatment with a new PET CT. One hundred and ninety three pts. have been evaluated. The median age at diagnosis was 29 years. One hundred and twenty five (65%) had localized stage (I-II) non bulky and 68 (35%) presented with advanced stage (III-IV), or bulky disease, 33 (17%) had bulky disease. RESULTS: One hundred and forty-eight (77%) achieved CR with negative PET-CT + 3. Forty-five (21%) were PET-CT+3 positive, 5 showed progressive disease. The other 40 pts. were in PR and completed a total of 6 ABVD + IFRT in PET-CT positive areas. Twenty eight achieved CR and 12 persisted with hypermetabolic lesions. Three died of progressive disease. After finishing planned treatment 178 pts. (92%) were in CR. With a median follow up of 39 months the EFS and OS at 36 months is 80% and 97% respectively. Patients with negative PET-CT +3 have an EFS of 86% compared to 61% for pts. with positive PET-CT+3 (P=0,001). We perform a multivariate analysis for EFS which included age, stage, IPS, bulky disease, extranodal areas and the result of the PET –CT+ 3. This last parameter together with age were the only ones with statistical significance (p=0.001 and 0.046 respectively). When comparing the results LH-05 with LH-96 there is no difference in EFS and OS at 36 months (83% vs. 85% and 97 vs. 96%) but in LH-05 only 23% received 6 cycles of ABVD and IFRT compared to 61% and 100% in LH-96. This reduces the exposure to chemo and radiotherapy. CONCLUSION: With PET-CT adapted therapy after 3 cycles of ABVD, 148 pts.(77%) received only 3 cycles of ABVD as initial therapy with an EFS and OS of 80% and 97% at 36 months. In the Cox regression model, PET-CT at completion of treatment was the most significant factor associated to EFS. In this interim analysis of PET-CT adapted therapy to all stages of HL, treatment with 3 cycles of ABVD can be adequate for pts. with negative PET-CT+3. Continuing with ABVD after a positive PET-CT +3 can be considered insufficient. A longer follow-up and a larger number of pts. are necessary to confirm these results. Disclosures: No relevant conflicts of interest to declare.

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COVID-19 Viral Load Not Associated with Disease Severity: Findings from A Retrospective Cohort Study

10.21203/rs.3.rs-144590/v1 ◽

2021 ◽

Author(s):

Abdulkarim Abdulrahman ◽

Saad Mallah ◽

Manaf AlQahtani

Keyword(s):

Cohort Study ◽

Viral Load ◽

Disease Severity ◽

Odds Ratio ◽

Retrospective Cohort ◽

Statistical Significance ◽

Rt Pcr ◽

Cross Sectional ◽

Viral Loads ◽

Using Data

Abstract Background: Being able to use COVID-19 RT-PCR Ct values as simple markers of disease outcome or prognosis would allow for the easy and proactive identification and triaging of high-risk cases. This study’s objective was thus to assess whether a correlation exists between COVID-19 viral loads, as indicated by RT-PCR Ct values, and disease severity, as indicated by respiratory indices Results: A multi-centre cross-sectional retrospective study was conducted, using data obtained from Bahrain’s National COVID-19 Task force’s centralised database. The study period was from May 2, 2020 to July 31, 2020. A multivariable logistic regression was used to assess for a correlation. The covariates adjusted for included sex, age, presentation, and comorbidities. In our cohort, Ct value showed no statistical significance for an association with requirement for oxygenation on admission (Odds ratio 1.046; 95%CI 0.999 to 1.096, p=0.054). Conclusion: Viral load, as indicated by Ct values, did not seem to be associated with requirement for oxygenation on admission in our cohort. We postulate however that time since onset of symptom may have acted as an unaccounted-for confounder.

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Different Clinical Features but Not Outcome in SLL Patients Compared to CLL,

Blood ◽

10.1182/blood.v118.21.3896.3896 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3896-3896

Author(s):

Alejandra Martinez-Trillos ◽

Eva Gine ◽

Jordina Rovira ◽

Marcos González ◽

Maria Jose Terol ◽

...

Keyword(s):

B Cells ◽

Median Time ◽

Who Classification ◽

Conflicts Of Interest ◽

Statistical Significance ◽

Biological Features ◽

Biological Variables ◽

Richter Syndrome ◽

Biological Studies

Abstract Abstract 3896 Chronic lymphocitytic leukaemia/Small lymphocytic lymphoma (CLL/SLL) is a neoplasm composed of monomorphic small neoplastic B cells that usually co-express CD5 and CD23. The current WHO classification considers CLL/SLL as the same entity being SLL the non-leukemic lymphoma presentation of CLL. The criteria for SLL include the presence of lymphadenopathy with less than 5×109/L peripheral blood B cells. Patients with SLL usually develop PB involvement during the evolution of the disease. The aim of this study was to analyze the main clinico-biological features and outcome of a series of SLL patients and compare them with the CLL patients diagnosed in the same period of time.Patients and methods: we have included 588 patients (353M/ 233F; median age 61 years) diagnosed with CLL or SLL according to the WHO classification criteria in the same period of time.The main clinico-biological features and the outcome were recorded and analysed according to the CLL/SLL diagnosis. Results: five hundred forty-five patients (93%) fulfil the criteria for CLL and 43 patients (7%) for SLL. The main clinico-biological variables according to the CLL/SLL criteria are detailed in the table. No differences were observed in gender distribution, age at diagnosis or ECOG. Patients with SLL had more frequently Binet C stage, low haemoglobin levels and platelet counts. 320 patients eventually received therapy, including purine analogues containing regimens (159 patients), chlorambucil (113), CHOP-like regimens (31), and other therapies (17). Sixty-nine patients received rituximab in combination. SLL patients received more frequently CHOP-like regimens than CLL patients, but this difference did not reach statistical significance. During the follow-up, 58% of the SLL patients eventually developed leukemic presentation, after a median time from diagnosis of 4.6 years (0.2–15 years). Patients with SLL not receiving treatment progressed to PB involvement sooner than treated SLL (median time, 1 year vs 6 year, respectively; p=0.06).Twenty four of the 588 patients eventually developed Richter syndrome, with this proportion being higher in the SLL than in CLL patients (13.1% vs 3.5%; p=0.001). Moreover, the proportion of second neoplasm (excluding non melanoma skin cancer) was higher for SLL patients than for CLL patients. After a median follow-up for surviving patients of 7.4 years (range, 0.1 to 28), 207 patients eventually died with no differences in overall survival between the two groups of patients. In addition, the causes of death were also similar (50% in SLL and 43% in CLL due to disease progression). In conclusion, although the outcome is similar in SLL and CLL groups, SLL patients more frequently had cytopenias as well as higher risk to develop Richter syndrome and second neoplasias. Genetic and other biological studies are warranted to elucidate the particular presentation and features of SLL.Patients (n=588)CLL (=545)SLL (n=43)pMedian age (years)6161Gender (Male/female)324/21929/14Binet C27/536 (5%)8/43 (18%)<0.001Hemoglobin <110 g/L26/526 (5%)7/39 (18%)0.001Platelets <100x109/L22/525 (4%)4/39 (10%)0.08High serum LDH (%)57/496 (11%)7/37 (18%)n.s.High B2 microglobuline191/442 (43%)17/32 (53%)n.s.High CD 38 expression135/484 (27%)18/38 (47%)0.011High ZAP 70 expression138/527 (26%)14/41 (34%)n.s.Unmutated IGHV160/335 (48%)10/15 (66%)n.s.Presence of Monoclonal Paraprotein28/545 (5%)4/43 (9%)n.s.Second Neoplasia (excluding Skin)74/545 (14%)11/43 (25%)0.03110-year risk of Richter Syndrome5.3%32.8%0.00110-year OS59%53.1%n.s. Disclosures: No relevant conflicts of interest to declare.

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Influence Of Antithymoglobulin Doses On The Outcome Of Hematopoietic Stem Cells Transplantations After a Flu-Bu2 Conditioning Regimen: A Retrospective Study On 168 Consecutive Patients

Blood ◽

10.1182/blood.v122.21.4547.4547 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4547-4547

Author(s):

Jérôme Cornillon ◽

Marie Balsat ◽

Aurélie Cabrespine ◽

Emmanuelle Tavernier ◽

Eric Hermet ◽

...

Keyword(s):

Infectious Disease ◽

Multivariate Analysis ◽

Retrospective Study ◽

Conflicts Of Interest ◽

Statistical Significance ◽

Conditioning Regimen ◽

Disease Free Survival ◽

Haematopoietic Stem Cell ◽

Hematopoietic Stem

Introduction Since the first descriptions by Slavin et al, indications of allogeneic haematopoietic stem cell transplantations (AHSCT) with fludarabine and busulfan conditioning regimen (CR) have increased. The use of strongly immunosuppressant products such as antithymocyte globulin (ATG) increase transplant engraftment and limit the risk of GVHD but with a higher risk of infectious complications. Recently, with myeloablative conditioning regimen (MAC), one randomized and one retrospective studies showed a reduction of cGVHD incidence (1,2). In reduced CR (RIC), the results are contradictory. In large series, the use of ATG seems to increase the relapse rate and ultimately influence the overall survival (OS) (3). Therefore, the ATG dose in RIC conditioning remains discussed. In order to clarify this point, we conducted a retrospective study on patients who received a fludarabine-busulfan RIC AHSCT with easer one or tow days of ATG. Methods 168 consecutive patients, followed between January 2000 and December 2011 in 2 French centers were analysed. RIC was based on Fludarabine 150 mg/m² and Busulfan for 2 consecutive days. Selected dose of ATG (Thymoglobuline®) administered were easer 2.5 or 5 mg/kg/day. Information concerning donors, recipients, conditioning regimen, graft harvesting and follow-up were collected using prospectively designed forms from Promise database. Results 108 patients had received 2.5 mg/kg (ATG1) versus 60 patients 5 mg/kg (ATG2). Median follow-up was of 60 months range [18-148]. Median age was 58 years with 99 males and 69 females. Diagnosis included AML/MDS (n=84), ALL (n=7), CML (n=7), lymphoma or CLL (n=52), and myeloma (n=18). Donors were matched sibling (n=74) or unrelated (n= 94). Only 6.5% of transplants were in HLA mismatch. Median time to recovery of polynuclear neutrophils was 17 days (range 3-73.2). Time to platelet reconstitution was 11 days (range 3-39). Median of OS was 39 months. In multivariate analysis, disease status at transplant, aGVHD severity (III-IV) (p=.000044; 3.52 (1.92-6.45) and cGVHD occurrence were the prognostic parameters statically significant. Median of Disease Free Survival (DFS) was 45 months (1-111) with no difference between ATG1 and ATG2 or other parameters. Death attributed to disease progression seemed to be higher in ATG1 group but difference failed to reach statistical significance (25% versus 17%, p=0.21). Incidence of non-relapse mortality (NRM) at 3 months was 5% and the global NRM at 26%. In multivariate analysis, two parameters influence significantly the NRM, the aGVHD incidence (III-IV) (p=.00016; 8.03(2.73-23.65)) and the dose of ATG delivered (31% vs. 16% for ATG2; p=.048; 2.36 (1.01-5.54)). Interesting, NRM was principally significant in late events (> 3 months) with more death by GVHD or infectious disease in ATG1 group. No difference between ATG1 and ATG2 group was noted for hematopoietic reconstitution, rejection rate (2 in each group of SAL) and incidence of aGvHD. Although cumulative incidence of cGvHD seemed to be higher in ATG1 group, difference failed to reach statistical significance (42% versus 33%, p=0.23). Conclusion Our result show that 2 days of ATG decrease NRM independently of disease, source of donor, graft or GVHD incidence without increasing the risk of relapse or infectious disease. These results are compatible with previous results observed with MAC. According to our results, in RIC, higher dose of ATG might be recommended. 1. Socie G, et al; Blood. 2011 Jun 9;117(23):6375–82. 2. Mohty M, et al; Leukemia. 2010 Sep 30;24(11):1867–74. 3. Soiffer RJ, et al. Blood. 2011 Jun 23;117(25):6963–70. Disclosures: No relevant conflicts of interest to declare.

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Impact Of Dedicated CML Clinic On The Outcome Of Patients With Newly Diagnosed CML: Experience Of a Single Canadian Center

Blood ◽

10.1182/blood.v122.21.5186.5186 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5186-5186

Author(s):

Moussab Damlaj ◽

Yury Monczak ◽

Sarit Assouline

Keyword(s):

Conflicts Of Interest ◽

Blast Crisis ◽

Retrospective Chart Review ◽

Rank Test ◽

Molecular Testing ◽

Inadequate Response ◽

Rt Pcr ◽

Molecular Responses ◽

Sokal Score

Abstract Background The outcome of patients with CML has improved significantly since the introduction of imatinib (O’Brien et al 2003). In the landmark IRIS trial, the rate of complete cytogenetic response (CCyR) was 69% by 12 months and 87% by 60 months and 7% of patients progressed to accelerated or blast crisis (Druker et al 2006). Multiple studies show that bcr-abl transcript level at 3 months can predict outcome and can be used to guide therapeutic strategies (Marin et al 2012). Additionally, patients achieving CCyR within 2 years on imatinib were projected to have a normal life expectancy (Gambacorti-Passerini et al 2011). Surprisingly, a survey of the CML World Registry involving over 1800 patients revealed that only 10% and 15% of patients had cytogenetic and molecular evaluation at 3 months, respectively. At our institution, we have a dedicated, multidisciplinary CML clinic with RT-PCR assay in house. We sought to determine how the outcome of our CP-CML patients, followed every 3 months and according to the ELN (European Leukemia Network) guidelines compares to clinical trial results. Methods Patients with CP-CML treated with imatinib first line between January 2004 and December 2012 were included in this retrospective chart review. Diagnosis was based on bone marrow aspirate with blast count and cytogenetic and/or FISH, and bcr/abl transcript RT-PCR using the IS method. Patients presenting in AP or BP, or those having previous lines of therapy except hydroxyurea or anagrelide were excluded. Baseline demographic, medical history, Sokal score at presentation and monitoring frequency for hematologic, cytogenetic and molecular responses were extracted. Definitions of cytogenetic and molecular responses were in accordance with the ELN guidelines. Cumulative rates of cytogenetic and molecular responses were estimated using the Kaplan–Meier method. Data for patients not achieving an adequate response were censored at the last follow up visit. Differences between groups were calculated by log rank test. The study received IRB approval at our institution. Results 55 eligible patients were identified. Median age was 53 years (17-92) and 33 (60%) were male. Distribution of Sokal score was low in 28 (50.9%), intermediate in 22 (40%) and high in 5 (9%). Median follow up duration was 53 months (range 3-106). Seven patients (12.7%) required switching to second line TKI, six for inadequate response, one for intolerance and one patient required switch to third line TKI for inadequate response. Molecular testing at 3 and 18 months post start of imatinib was performed in 48 pts (87.3%) and 53 (96.4%), respectively. At 12 months, 49 (89.1%) had cytogenetic evaluation. Estimated rates of CCyR at 6 months, 12 months, 18 months and 24 months were 46.6%, 69.2%, 78.7% and 88.2%, respectively. Estimated rates of MMR at 6 months, 12 months, 18 months and 24 months were 23.9%, 41.2%, 58.8% and 70.6%, respectively. When stratified by Sokal score, rate of CCyR at 12 months was 82.1%, 72.7% and 60% (p 0.8840) for low, intermediate and high scores, respectively. Conclusions CP-CML patients followed in a dedicated CML clinic receive more rigorous follow-up and monitoring and achieve response rates similar to that of clinical trials. Additionally, in this small cohort of patients, discontinuation rate of imatinib was substantially lower than previously reported. Disclosures: No relevant conflicts of interest to declare.

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Treatment of patients with Schistosomiasis mansoni: a double blind clinical trial comparing praziquantel with oxamniquine

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46651986000300007 ◽

1986 ◽

Vol 28 (3) ◽

pp. 174-180 ◽

Cited By ~ 15

Author(s):

Luiz Caetano da Silva ◽

José Murilo R. Zeitune ◽

Lucia Maria F. Rosa-Eid ◽

Dirce Mary C. Lima ◽

Rita H. Antonelli ◽

...

Keyword(s):

Clinical Trial ◽

Side Effects ◽

Statistical Significance ◽

Double Blind ◽

Chemical Structures ◽

Double Blind Clinical Trial ◽

Negative Findings ◽

Rectal Biopsies ◽

Cure Rates

A double-blind clinical trial involving 120 patients with chronic schistosomiasis was carried out to compare the tolerability and efficacy of praziquantel and oxamniquine. The patients were randomly allocated into two groups. One was treated with praziquantel, 55 mg/kg of body weight CBWT), and the other one with oxamniquine, 15mg/kg bwt, administered in a single oral dose. The diagnosis and the parasitological follow-up was based on stool examinations by quantitative Kato-Katz method and on rectal biopsies. Side-effects — mainly dizziness, sleepness, abdominal distress, headache, nausea and diarrhea — were observed in 87% of the cases. Their incidence, intensity and duration were similar for both drugs but abdominal pain was significantly more frequent after praziquantel intake and severe dizziness was more commonly reported after oxamniquine. A significant increase of alanine-aminotransferase and y-glutamyltransferase was found with the latter drug and of total bilirubin with the former one. A total of 48 patients treated with praziquantel and 46 with oxamniquine completed with negative findings the required three post-treatment parasitological controls — three slides of each stool sample on the first, third and sixth month. The achieved cure rates were 79.2% and 84.8%, respectively, a difference without statistical significance. The non-cured cases showed a mean reduction in the number of eggs per gram of feces of 93.5% after praziquantel and of 84.1% after oxamniquine. This diference also was not significant. Five patients retreated with praziquantel were cured but only one out of three treated a second time with oxamniquine. These findings show that both drugs — despite their different chemical structures, pharmacological properties and mechanisms-of-action — induce similar side-effects as well as a comparable therapeutical efficacy, in agreement with the results reported from analogous investigations.

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COVID-19 viral load not associated with disease severity: findings from a retrospective cohort study

BMC Infectious Diseases ◽

10.1186/s12879-021-06376-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Abdulkarim Abdulrahman ◽

Saad I. Mallah ◽

Manaf Alqahtani

Keyword(s):

Viral Load ◽

Disease Severity ◽

Retrospective Cohort ◽

Statistical Significance ◽

Clinical Markers ◽

Rt Pcr ◽

Clinical Tool ◽

Cross Sectional ◽

Viral Loads ◽

Using Data

Abstract Background Being able to use COVID-19 RT-PCR Ct values as simple clinical markers of disease outcome or prognosis would allow for the easy and proactive identification and triaging of high-risk cases. This study’s objective was thus to explore whether a correlation exists between COVID-19 viral loads, as indicated by RT-PCR Ct values, and disease severity, as indicated by respiratory indices. Results A multi-centre cross-sectional retrospective study was conducted, using data obtained from Bahrain’s National COVID-19 Task force’s centralised database. The study period ranged from May 2, 2020 to July 31, 2020. A multivariable logistic regression was used to assess for a correlation using data from a total of 1057 admitted COVID-19 cases. The covariates adjusted for included sex, age, presentation, and comorbidities. In our cohort, Ct value showed no statistical significance for an association with requirement for oxygenation on admission (Odds ratio 1.046; 95%CI 0.999 to 1.096, p = 0.054). Conclusion Viral load, as indicated by Ct values, did not seem to be associated with requirement for oxygenation on admission in our cohort. We postulate however that time since onset of symptom may have acted as an unaccounted-for confounder. As such, RT-PCR Ct values may not be a useful prognostic clinical tool in isolation.

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Smouldering Adult T-Cell Leukaemia/Lymphoma (ATLL) Is Not Associated with An Increased Risk of Aggressive ATLL In HTLV-1 Positive Patients

Blood ◽

10.1182/blood.v116.21.4167.4167 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4167-4167 ◽

Cited By ~ 1

Author(s):

Andrew Hodson ◽

Barbara Bain ◽

Paul Fields ◽

Graham Talyor

Keyword(s):

Viral Load ◽

T Cell ◽

Lymphocyte Count ◽

Proviral Load ◽

Conflicts Of Interest ◽

Organ Involvement ◽

Cell Leukaemia ◽

Total Lymphocyte ◽

Increased Risk

Abstract Abstract 4167 Introduction: Criteria for the diagnosis of smouldering adult T-cell leukaemia/lymphoma (ATLL) are the detection of anti-HTLV-1 antibodies, total lymphocyte count <4×109/L, ≥ 5% abnormal lymphocytes of T cell nature in the peripheral blood, normal corrected calcium and LDH <1.5 times the upper limit of normal. Skin or lung involvement may be present but no other organ involvement is permitted. Smouldering ATLL has been associated with 2 and 4 year survival of 77.7% and 62.8% respectively. Aim: To identify whether patients meeting the diagnostic criteria for smouldering ATLL are at increased risk of aggressive ATLL. Methods: A retrospective analysis of patients referred to the National Centre for Human Retrovirology, London between 1991 and 2007, excluding those diagnosed with ATLL prior to referral. Demographic and clinical data were collected at initial review. HTLV-I viral DNA was quantified by real-time PCR. Results: Blood films were reported for 150 new HTLV-1 infected patients, 114 female and 36 male, the majority of Afro-Caribbean or African origin. Median follow up was 3.7 years.92 (61%) were asymptomatic HTLV-1 carriers (ACs) and 58 (39%) had HTLV-associated inflammatory disease (HAID) of which HTLV associated myelopathy (HAM) accounted for the majority (n = 54). ≥5% abnormal lymphocytes were documented in 43 (29%) in whom the percentage of abnormal lymphocytes was significantly higher in those patients with HAID than ACs (p=0.006) although the total lymphocyte counts were similar in the two groups. Globulin, creatine kinase (CK), lactate dehydrogenase (LDH) and beta 2 microglobulin (β2M) were all higher in the HAID group. HTLV-1 viral load was significantly higher in males than in females and in those with HAID. On multivariate analysis β2M was independently predictive of disease status between ACs and HAID. Overall abnormal lymphocytes were observed in the blood of 75% of patients. An irregular or convoluted nucleus was the most frequent abnormality while cleft or bi-lobed nuclei, large granular lymphocytes, flower cells and abnormally large lymphocytes were also observed. Flower cells were identified in 17% of cases and their presence was associated with both a higher overall percentage of abnormal lymphocytes and viral load (% abnormal lymphocytes 4% v 2%, p=0.008; viral load 9.3% v 4.5%, p=0.048). Three patients (2%) developed aggressive ATLL, in all cases lymphomatous, after 2.8, 6.4 and 10 years follow up. Only one had ≥5% abnormal lymphocytes but all had viral load ≥10% at presentation. Two had HAID while one was an AC. The incidence of aggressive ATLL in this cohort was 4.1 cases per 1000 person-years (95% CI 0.83 – 11.9) equating to four cases per 100 HTLV-1 carriers per decade. No patient with HTLV-1 proviral load <10% developed aggressive ATLL. Conclusion: In this cohort fulfilment of the Shimoyama classification for smouldering ATLL was not associated with an increased risk of developing aggressive ATLL (1/43 v 2/107) during a median of 3.7 years of follow up. We therefore propose that ATLL should not be diagnosed in the absence of a raised lymphocyte count and/or organ involvement. However HTLV-1 proviral load does appear to be an important predictor for risk of ATLL and further study to identify patients at risk prior to development of this aggressive malignancy is warranted. Disclosures: No relevant conflicts of interest to declare.

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