scholarly journals Outcomes of Patients with Hematologic Malignancies and COVID-19: Perspective of a Large Hematology Center in Greece

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4992-4992
Author(s):  
Nikolaos Spyridis ◽  
Georgios Karavalakis ◽  
Despina Mallouri ◽  
Ioannis Eftychidis ◽  
Panagiotis Dolgyras ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Death Rate ◽  
Anticancer Therapy ◽  
Rt Pcr ◽  
Hematologic Disease ◽  
Acute Leukemias ◽  
Hematologic Diseases ◽  
Icu Admission ◽  
Treatment Status ◽  
Autologous Hct

Abstract The emergence of SARS-CoV-2, as of July 2021 has affected 469,042 individuals and accounted for 12,851 deaths nationally in Greece, according to WHO database. Mortality rate is higher in elderly patients (pts) and in pts with comorbidities, including malignancies. However, there is a growing interest on COVID-19 outcomes in pts with hematologic diseases. The aim of this study was to perform a systematic registration and analysis of the outcomes of pts with hematologic disease and COVID-19 in our center. The study is a single-center, retrospective study, conducted at a Hematology Department and HCT unit of a tertiary Hospital after approval from local Ethics Committee. We included pts with a hematologic disease and RT-PCR confirmed COVID-19 infection between October 2020 and July 2021. We reviewed hematological medical records to extract demographic and clinical data of COVID-19 infections. Most of the data have already been intergraded in ASH Research Collaborative Data Hub. Hematologic diseases were categorized to: Acute Myeloblastic Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), Non-Hodgkin Lymphomas (NHL), Chronic Lymphocytic Leukemia (CLL), Hodgkin Lymphoma (HL), Multiple Myeloma (MM), Myelodysplastic Syndromes (MDS), Chronic Myeloid Leukemia (CML), Myeloproliferative Neoplasms (MPN, including all Philadelphia-negative MPN) and other hematologic conditions. We evaluated a total of 89 pts, 54% were male and 46% female, with a median age of 64.5 (20-86) and 59.5 (21-85) years respectively. 83% of pts were ≥40 years and 27% ≥70 years old. Most of them (92%) acquired infection outside a hospital setting. 13% of pts were asymptomatic and diagnosis was confirmed only with positive RT-PCR test. The most common represented malignancies were NHL 26%, CLL 20% and acute leukemias 13.5%, while 15% of pts underwent transplantation (HCT). Pts presented with moderate/severe COVID-19 were 55%, while 43% of hospitalized pts required Intensive Care Unit (ICU) admission. Overall, the death rate was 24%, while remarkably almost all pts required ICU support did not survive (mortality 94%). Higher mortality observed in patients with MDS (50%), MM (43%), CLL (39%), ALL (33%) and NHL (30%). Further analysis showed a positive correlation between mortality and male gender with 16 deaths out of 21 (p = .0245), as well as mortality and ICU admission (p < .001). A chi-square test of independence was performed to examine the relation between age and COVID-19 severity, without any statistically significant result [x 2 (2, N = 87) = 3.475, p = .176]. Whereas the only significant correlation between age and mortality was among age groups 18-39 and >70 years (p = .0146). Regarding treatment, pts were divided into two subgroups, 78% of them received anticancer therapy at least once in their lives, while 22% of them have never been on treatment, mainly pts with CLL and indolent NHL. 62% of the first subgroup manifested moderate/severe COVID-19 infection requiring hospitalization with 28% death rate, while the same rates in the 2 nd subgroup were 30% and 10% respectively. Although there was a significant correlation between the treatment status and the severity of COVID-19 infection (p = .020), the above was not translated in statistically higher death rate in the first subgroup (p = .14). There was also a correlation between HCT and COVID-19 severity in general (p = .005), with autologous HCT having statistically higher mortality than the allogeneic subgroup (p = .032). Α similar analysis in CLL and NHL groups showed no relation among treatment status, COVID-19 severity, and mortality (p values .638 and .115/ .34 and .62 respectively). As anticipated in hematological pts, the immunocompromised nature of the underlying disease makes them extremely vulnerable to COVID-19 infection regardless of their treatment status, a fact that is also reflected in mortality despite ICU admission and support. In general, the severity of infection is correlated to anticancer therapy, while mortality to male sex, ICU admission and autologous HCT. Larger number of pts are necessary for further studies to better understand the parameters that impact the outcome of COVID-19 in hematological pts. Hematology departments should remain COVID-19 free zones, dedicated only to hematologic treatment and pts should strictly comply with social distancing. It remains to see if vaccines can play a key role to protect this special group of pts. Figure 1 Figure 1. Disclosures Anagnostopoulos: Abbvie: Other: clinical trials; Sanofi: Other: clinical trials ; Ocopeptides: Other: clinical trials ; GSK: Other: clinical trials; Incyte: Other: clinical trials ; Takeda: Other: clinical trials ; Amgen: Other: clinical trials ; Janssen: Other: clinical trials; novartis: Other: clinical trials; Celgene: Other: clinical trials; Roche: Other: clinical trials; Astellas: Other: clinical trials .

scholarly journals Patient-reported outcomes in drug development for hematology

Hematology ◽  
2015 ◽  
Vol 2015 (1) ◽  
pp. 496-500 ◽  
Author(s):  
Catherine Acquadro ◽  
Antoine Regnault
Keyword(s):  
Clinical Trials ◽  
Drug Development ◽  
Patient Reported Outcomes ◽  
Clinical Decision Making ◽  
Well Being ◽  
New Drugs ◽  
Specific Situation ◽  
Treatment Benefit ◽  
Hematologic Diseases ◽  
Patient Reported

Abstract Patient-reported outcomes (PROs) are any outcome evaluated directly by the patient himself and based on the patient's perception of a disease and its treatment(s). PROs are direct outcome measures that can be used as clinical meaningful endpoints to characterize treatment benefit. They provide unique and important information about the effect of treatment from a patient's view. However, PROs will only be considered adequate if the assessment is well-defined and reliable. In 2009, the FDA has issued a guidance, which defines good measurement principles to consider for PRO measures intended to give evidence of treatment benefit in drug development. In hematologic clinical trials, when applied rigorously, they may be used to evaluate overall treatment effectiveness, treatment toxicity, and quality of patient's well-being at short-term and long-term after treatment from a patient's perspective. In situations in which multiple treatment options exist with similar survival outcome or if a new therapeutic strategy needs to be evaluated, the inclusion of PROs as an endpoint can provide additional data and help in clinical decision making. Given the diversity of the hematological field, the approach to measurement needs to be tailored for each specific situation. The importance of PROs in hematologic diseases has been highlighted in a number of international recommendations. In addition, new perspectives in the regulatory field will enhance the inclusion of PRO endpoints in clinical trials in hematology, allowing the voice of the patients with hematologic diseases to be taken into greater consideration in the development of new drugs.

scholarly journals Managing Clinical Trials for Alzheimer’s Disease During the COVID-19 Crisis: Experience at Fundació ACE in Barcelona, Spain

2020 ◽  
Vol 77 (4) ◽  
pp. 1805-1813
Author(s):  
Carla Abdelnour ◽  
Ester Esteban de Antonio ◽  
Alba Pérez-Cordón ◽  
Asunción Lafuente ◽  
Mar Buendía ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Ad Hoc ◽  
Strategic Plan ◽  
Lessons Learned ◽  
Drop Out ◽  
Rt Pcr ◽  
Serological Tests ◽  
Clinical Trial Research ◽  
Research Activities ◽  
The Impact

Background: The COVID-19 pandemic has brought great disruption to health systems worldwide. This affected ongoing clinical research, particularly among those most vulnerable to the pandemic, like dementia patients. Fundació ACE is a research center and memory clinic based in Barcelona, Spain, one of the hardest-hit countries. Objective: To describe the ad-hoc strategic plan developed to cope with this crisis and to share its outcomes. Methods: We describe participants’ clinical and demographic features. Additionally, we explain our strategic plan aimed at minimizing the impact on clinical trial research activities, which included SARS-CoV-2 RT-PCR and IgG serological tests to all participants and personnel. The outcomes of the plan are described in terms of observed safety events and drop-outs during the study period. Results: A total of 130 patients were participating in 16 active clinical trials in Fundació ACE when the lockdown was established. During the confinement, we performed 1018 calls to the participants, which led to identify adverse events in 26 and COVID-19 symptoms in 6. A total of 83 patients (64%) could restart on-site visits as early as May 11, 2020. All SARS-CoV-2 RT-PCR diagnostic tests performed before on-site visits were negative and only three IgG serological tests were positive. Throughout the study period, we only observed one drop-out, due to an adverse event unrelated to COVID-19. Discussion: The plan implemented by Fundació ACE was able to preserve safety and integrity of ongoing clinical trials. We must use the lessons learned from the pandemic and design crisis-proof protocols for clinical trials.

scholarly journals A prospective clinical pilot study on the effects of a hydrogen peroxide mouthrinse on the intraoral viral load of SARS-CoV-2

2020 ◽  
Vol 24 (10) ◽  
pp. 3707-3713
Author(s):  
Maximilian J. Gottsauner ◽  
Ioannis Michaelides ◽  
Barbara Schmidt ◽  
Konstantin J. Scholz ◽  
Wolfgang Buchalla ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Clinical Trials ◽  
Viral Load ◽  
Pilot Study ◽  
High Risk ◽  
Infection Prevention ◽  
Healthcare Professionals ◽  
Patient Contact ◽  
Rt Pcr ◽  
Virus Culture

Abstract Objectives SARS-CoV-2 is mainly transmitted by inhalation of droplets and aerosols. This puts healthcare professionals from specialties with close patient contact at high risk of nosocomial infections with SARS-CoV-2. In this context, preprocedural mouthrinses with hydrogen peroxide have been recommended before conducting intraoral procedures. Therefore, the aim of this study was to investigate the effects of a 1% hydrogen peroxide mouthrinse on reducing the intraoral SARS-CoV-2 load. Methods Twelve out of 98 initially screened hospitalized SARS-CoV-2-positive patients were included in this study. Intraoral viral load was determined by RT-PCR at baseline, whereupon patients had to gargle mouth and throat with 20 mL of 1% hydrogen peroxide for 30 s. After 30 min, a second examination of intraoral viral load was performed by RT-PCR. Furthermore, virus culture was performed for specimens exhibiting viral load of at least 103 RNA copies/mL at baseline. Results Ten out of the 12 initially included SARS-CoV-2-positive patients completed the study. The hydrogen peroxide mouthrinse led to no significant reduction of intraoral viral load. Replicating virus could only be determined from one baseline specimen. Conclusion A 1% hydrogen peroxide mouthrinse does not reduce the intraoral viral load in SARS-CoV-2-positive subjects. However, virus culture did not yield any indication on the effects of the mouthrinse on the infectivity of the detected RNA copies. Clinical relevance The recommendation of a preprocedural mouthrinse with hydrogen peroxide before intraoral procedures is questionable and thus should not be supported any longer, but strict infection prevention regimens are of paramount importance. Trial registration German Clinical Trials Register (ref. DRKS00022484)

Differential Expression of ERG Isoforms in Acute Myeloid and T-Lymphoblastic Leukemia Is Regulated by DNA-Methylation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2126-2126
Author(s):  
Claudia D. Baldus ◽  
Cornelia Schlee ◽  
Julia Thibaut ◽  
Sandra Heesch ◽  
Arend Bohne ◽  
...  
Keyword(s):  
Differential Expression ◽  
Cpg Island ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Rt Pcr ◽  
Acute Leukemias ◽  
Aberrant Expression ◽  
Cd34 Cells ◽  
Exon 4 ◽  
Acute Myeloid

Abstract The oncogenic ETS transcription factor ERG is involved in various cellular pathways including developmental regulation, proliferation, and differentiation. In hematopoiesis ERG plays a specific role during normal T-cell differentiation showing high expression levels in stem cells and down regulation in the progenitor compartment. In this regard, it is intriguing that aberrant expression of ERG was found in a subset of patients with acute T-lymphoblastic leukemia (T-ALL) and was associated with an inferior outcome. Furthermore, high level ERG expression was of adverse prognostic significance in patients with newly diagnosed acute myeloid leukemia (AML), thus highlighting ERG’s potential role in myeloid as well as T-lineage leukemogenesis. ERG3 (NM_182918) and ERG2 (NM_004449) represent the main isoforms and show abundant expression in myeloid and lymphoid hematopoietic progenitor cells. The expression pattern of specific ERG isoforms in acute leukemias has yet to be investigated. To further elucidate the nature of aberrant ERG expression we have determined the existence and transcriptional regulation of ERG isoforms in pretreatment bone marrow samples of adult T-ALL (n=21) and AML (n=20) patients as well as in normal CD34+ hematopoietic cells of healthy volunteers (n=5). 5′RACE revealed the presence of a new ERG isoform (ERG3Δex12) characterized by expression of exon 5 and absence of exon 12. Expression of ERG3Δex12 was verified by RT-PCR in AML, T-ALL, and CD34+ cells. In addition, real-time RT-PCR showed concomitant expression of the two main isoforms ERG2 and ERG3 in AML and normal CD34+ cells. In contrast, T-ALL patients lacked expression of ERG isoforms harboring exon 4 (ERG2). Promoter analyses of ERG2 and ERG3 revealed the presence of two CpG islands in the ERG2 promoter region, whereas no CpG island was predicted in the ERG3 promoter. Bisulfit conversion of genomic DNA and sequencing of cloned PCR products revealed a significantly higher degree of methylation of CpG island 2 in T-ALL samples (median: 86.4%, range: 16.0 – 98.8%) as compared to AML (median: 38.1%, range: 10.9 – 60.7%; P-value=0.0002 - two sided T-test). As for CpG island 1, CD34+ cells had the lowest rate of methylation in CpG island 2 (median: 7.7%, range: 2.4 – 20.7%). Thus, the differential expression of ERG isoforms is mediated by epigenetic silencing of exon 4 containing transcripts in T-ALL. In conclusion, the identification of the new ERG isoform (ERG3Δex12) suggests the association with different partners as the central exons, including exon 12, guide the interaction with different proteins. Furthermore, the distinct expression of specific ERG transcripts controlled by methylation adds to the complexity of ERG directed downstream pathways in different leukemic subtypes.

A Population-Based Study In Acute Promyelocytic Leukemia (APL) Suggests a Higher Early Death Rate and Lower Overall Survival Than Commonly Reported In Clinical Trials: Data From the Surveillance, Epidemiology, and End Results (SEER) Program and the New York State Cancer Registry In the United States Between 1992–2007

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 872-872 ◽  
Author(s):  
Jae H. Park ◽  
Katherine S Panageas ◽  
Maria J Schymura ◽  
Baozhen Qiao ◽  
Joseph G Jurcic ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Rural Areas ◽  
Death Rate ◽  
Early Death ◽  
The United States ◽  
Population Based ◽  
Seer Program ◽  
Newly Diagnosed ◽  
True Rate ◽  
Over Time

Abstract Abstract 872 Background: All-trans retinoic acid (ATRA) with contemporary therapeutic strategies for the treatment of patients with newly diagnosed acute promyelocytic leukemia (APL) have dramatically improved outcome. Currently, the major cause for treatment failure is death during induction mostly due to hemorrhage, infection and differentiation syndrome. Since there is virtually no primary resistance to induction and the relapse rate once in complete remission (CR) is very low, reducing the early death rate would be critical to further improve the cure rate. The true rate of early death in the United States (US) is not yet clear. Cooperative group multicenter studies report early death rates of 5–10% within 1 month of starting therapy which is likely an underestimation, in part, due to failure to account for those who die prior to registration on study or possibly other selection biases for enrollment. Methods: We performed an epidemiologic study of the true rate of early death and overall survival (OS) using US population-based datasets of all newly diagnosed patients with APL. The datasets from SEER Program 13 (includes 5 states: Connecticut, Hawaii, Iowa, New Mexico and Utah; 8 metropolitan areas including Detroit, Atlanta, San Francisco-Oakland, Seattle-Puget Sound, Los Angeles, San Jose-Monterey, Alaska Native Registry and rural Georgia) and the New York (NY) State Cancer Registry were used to identify patients with APL registered in the US and NY state from January 1, 1992 to December 31, 2007. Patterns of APL incidence, early death rate, long-term OS over time, and differences in OS by region (urban vs. rural) were analyzed in pre-set time periods of 1992–1996, 1997–2001, and 2002–2007. Results: A total of 1,400 and 721 patients with APL were identified in the SEER program and the NY registry, respectively. The number of registered APL patients was similar between men and women in both datasets, and has steadily increased from 1992–1996 (295 cases in SEER and 143 in NY) to 2002–2007 (681 cases in SEER and 371 in NY). Early death rate, defined as death reported within the first month of diagnosis, was 22.7% in the years 1992–1996, 15.6% in 1997–2001, and 18.1% in 2002–2007 in the SEER program, and 10.9%, 11.9% and 11.2% in the NY registry. No significant differences in the early death rate were observed between urban and rural areas in either datasets. OS at 1 year improved from 59.8% in 1992–1996 to 69.6% in 1997–2001; at 2 years from 53.7% to 65.3%; and at 3 years from 50.2% to 63.7% in the datasets from the SEER program. There were no significant changes in OS from 1997–2001 to 2002–2007, and similar trends in OS were observed in the NY datasets (Figure). Interestingly, when the survival data were analyzed by the urban/rural regions in the SEER program, the greatest improvement was observed in patients treated in the urban counties with absolute increases in 2- and 3-year OS of 15.3% (from 53.1 in 1992–1996 to 68.4% in 2002–2007) and 17.6% (from 49.8 to 67.4%), respectively. In contrast, in patients treated in rural counties, increases in 0.4% (from 62.5 in 1992–1996 to 62.9% in 2002–2007) and 7.3% (from 55.6 to 62.9%) were observed in 2- and 3-year OS, respectively. However, the latter statement should be interpreted with caution since the rural OS estimates are imprecise due to small numbers. Conclusions: The large number of newly diagnosed APL patients and the long follow-up reported here confirm improvement in OS over time in a US population-based study. Disappointingly, the early death rate has changed only modestly since 1992 (22.7% in 1992–1996, and 18.1% in 2002–2007), and appears significantly higher than what is reported in contemporary clinical trials. Furthermore, the long-term OS, though improved over time, appears lower than that reported in clinical trials. In fact, more than 25% of patients are not cured of their disease. OS in patients treated in rural areas appears worse, possibly related, in part, to less access to specialized centers, although the analysis is limited due to small numbers. Strategies to reduce the early death rate in APL and improve OS should include very early introduction of ATRA, arsenic trioxide or both and aggressive blood product support at the very first suspicion of the diagnosis well before genetic confirmation. Disclosures: No relevant conflicts of interest to declare.

Palliative care physicians' beliefs toward hematology and the care of patients with hematologic diseases: Results of a nationwide survey.

2018 ◽  
Vol 36 (34_suppl) ◽  
pp. 95-95
Author(s):  
Wil Leonard Santivasi ◽  
Kelly Wu ◽  
Mark Robert Litzow ◽  
Thomas William LeBlanc ◽  
Jacob J Strand
Keyword(s):  
Palliative Care ◽  
Regression Models ◽  
Nationwide Survey ◽  
Correlated Data ◽  
Statistical Testing ◽  
Hematologic Disease ◽  
Hematopoietic Stem ◽  
Hematologic Diseases ◽  
Logistic Regression Models ◽  
Physician Contact

95 Background: Palliative care (PC) specialists provide supportive care for patients with hematologic diseases (HD). However, the degree of engagement by PC physicians may be limited by the views of both PC physicians & hematologists. Prior studies have surveyed hematologists to identify barriers to delivery of PC, however PC physician views are unclear. This study aimed to examine views of PC physicians toward hematology. Methods: A survey was mailed to a random sample of the AAHPM physician contact list in 2017. Items focused on perceptions of their understanding of HD, comfort providing care, opinions regarding PC & hospice involvement, & beliefs about hematologists. Anonymized responses were assessed on a Likert scale. Statistical testing was based on logistic regression models with generalized estimating equations to account for correlated data within respondents. Results: 538 of 1000 surveys were completed. 51.9% of respondents were male. Community (37.2%), academic (36.7%) & hospice (26.2%) physicians were represented. Respondents were likelier to believe they understand the trajectories of lymphoma & myeloma than leukemia or patients undergoing hematopoietic stem cell transplantation (HSCT) (p < 0.001). They were more comfortable discussing prognosis (p < 0.001) & managing symptoms (p < 0.001) in lymphoma & myeloma than leukemia & HSCT. They were likelier to believe that hematologists’ perceptions of PC physicians limit collaboration rather than their own views of hematologists (p < 0.001). 80.2% agreed that hospice referrals are not made early enough. Conclusions: PC physicians’ understanding of trajectories & comfort caring for patients varies by hematologic disease. They perceive that hematologists’ perceptions are a larger barrier than their own & hospice referrals are delayed. These results provide insights into opportunities for better collaboration with hematologists.

Role of autophagy in cancer prevention, development and therapy

2013 ◽  
Vol 55 ◽  
pp. 133-151 ◽  
Author(s):  
G. Vignir Helgason ◽  
Tessa L. Holyoake ◽  
Kevin M. Ryan
Keyword(s):  
Quality Control ◽  
Clinical Trials ◽  
Cancer Prevention ◽  
Mammalian Cells ◽  
Physiological Role ◽  
Anticancer Therapy ◽  
Substantial Progress ◽  
Health And Disease ◽  
Made In

Autophagy is a process that takes place in all mammalian cells and ensures homoeostasis and quality control. The term autophagy [self (auto)-eating (phagy)] was first introduced in 1963 by Christian de Duve, who discovered the involvement of lysosomes in the autophagy process. Since then, substantial progress has been made in understanding the molecular mechanism and signalling regulation of autophagy and several reviews have been published that comprehensively summarize these findings. The role of autophagy in cancer has received a lot of attention in the last few years and autophagy modulators are now being tested in several clinical trials. In the present chapter we aim to give a brief overview of recent findings regarding the mechanism and key regulators of autophagy and discuss the important physiological role of mammalian autophagy in health and disease. Particular focus is given to the role of autophagy in cancer prevention, development and in response to anticancer therapy. In this regard, we also give an updated list and discuss current clinical trials that aim to modulate autophagy, alone or in combination with radio-, chemo- or targeted therapy, for enhanced anticancer intervention.

Evidence-based RT-PCR methods for the detection of the 8 most common MLL aberrations in acute leukemias

2015 ◽  
Vol 39 (2) ◽  
pp. 242-247 ◽  
Author(s):  
Thomas Burmeister ◽  
Claus Meyer ◽  
Daniela Gröger ◽  
Julia Hofmann ◽  
Rolf Marschalek
Keyword(s):  
Evidence Based ◽  
Rt Pcr ◽  
Acute Leukemias
Sign in / Sign up

Export Citation Format

Share Document