Publications by authors named "Anat Halevy"

4 Publications

  • Page 1 of 1

Immune profile differences between chronic GVHD and late acute GVHD: results of the ABLE/PBMTC 1202 studies.

Blood 2020 04;135(15):1287-1298

CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada.

Human graft-versus-host disease (GVHD) biology beyond 3 months after hematopoietic stem cell transplantation (HSCT) is complex. The Applied Biomarker in Late Effects of Childhood Cancer study (ABLE/PBMTC1202, NCT02067832) evaluated the immune profiles in chronic GVHD (cGVHD) and late acute GVHD (L-aGVHD). Peripheral blood immune cell and plasma markers were analyzed at day 100 post-HSCT and correlated with GVHD diagnosed according to the National Institutes of Health consensus criteria (NIH-CC) for cGVHD. Of 302 children enrolled, 241 were evaluable as L-aGVHD, cGVHD, active L-aGVHD or cGVHD, and no cGVHD/L-aGVHD. Significant marker differences, adjusted for major clinical factors, were defined as meeting all 3 criteria: receiver-operating characteristic area under the curve ≥0.60, P ≤ .05, and effect ratio ≥1.3 or ≤0.75. Patients with only distinctive features but determined as cGVHD by the adjudication committee (non-NIH-CC) had immune profiles similar to NIH-CC. Both cGVHD and L-aGVHD had decreased transitional B cells and increased cytolytic natural killer (NK) cells. cGVHD had additional abnormalities, with increased activated T cells, naive helper T (Th) and cytotoxic T cells, loss of CD56bright regulatory NK cells, and increased ST2 and soluble CD13. Active L-aGVHD before day 114 had additional abnormalities in naive Th, naive regulatory T (Treg) cell populations, and cytokines, and active cGVHD had an increase in PD-1- and a decrease in PD-1+ memory Treg cells. Unsupervised analysis appeared to show a progression of immune abnormalities from no cGVHD/L-aGVHD to L-aGVHD, with the most complex pattern in cGVHD. Comprehensive immune profiling will allow us to better understand how to minimize L-aGVHD and cGVHD. Further confirmation in adult and pediatric cohorts is needed.
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http://dx.doi.org/10.1182/blood.2019003186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146024PMC
April 2020

Benefits and challenges with diagnosing chronic and late acute GVHD in children using the NIH consensus criteria.

Blood 2019 07 1;134(3):304-316. Epub 2019 May 1.

British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.

Chronic graft-versus-host disease (cGVHD) and late acute graft-versus-host disease (L-aGVHD) are understudied complications of allogeneic hematopoietic stem cell transplantation in children. The National Institutes of Health Consensus Criteria (NIH-CC) were designed to improve the diagnostic accuracy of cGVHD and to better classify graft-versus-host disease (GVHD) syndromes but have not been validated in patients <18 years of age. The objectives of this prospective multi-institution study were to determine: (1) whether the NIH-CC could be used to diagnose pediatric cGVHD and whether the criteria operationalize well in a multi-institution study; (2) the frequency of cGVHD and L-aGVHD in children using the NIH-CC; and (3) the clinical features and risk factors for cGVHD and L-aGVHD using the NIH-CC. Twenty-seven transplant centers enrolled 302 patients <18 years of age before conditioning and prospectively followed them for 1 year posttransplant for development of cGVHD. Centers justified their cGVHD diagnosis according to the NIH-CC using central review and a study adjudication committee. A total of 28.2% of reported cGVHD cases was reclassified, usually as L-aGVHD, following study committee review. Similar incidence of cGVHD and L-aGVHD was found (21% and 24.7%, respectively). The most common organs involved with diagnostic or distinctive manifestations of cGVHD in children include the mouth, skin, eyes, and lungs. Importantly, the 2014 NIH-CC for bronchiolitis obliterans syndrome perform poorly in children. Past acute GVHD and peripheral blood grafts are major risk factors for cGVHD and L-aGVHD, with recipients ≥12 years of age being at risk for cGVHD. Applying the NIH-CC in pediatrics is feasible and reliable; however, further refinement of the criteria specifically for children is needed.
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http://dx.doi.org/10.1182/blood.2019000216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911839PMC
July 2019

Prophylactic SSRI treatment for women suffering from mood and anxiety symptoms undergoing in vitro fertilization-a prospective placebo-controlled study.

Arch Womens Ment Health 2019 08 17;22(4):503-510. Epub 2018 Sep 17.

Department of Psychiatry, Tel Aviv Sourasky Medical Center, Tel Aviv-Yafo, Israel.

To explore the mood protective effect of prophylactic SSRI treatment on women undergoing IVF suffering from moderate affective and anxiety symptoms. In a randomized double blind, placebo-controlled, parallel design study, 41 women diagnosed with an Adjustment Disorder, who were undergoing IVF treatments, were randomized into two groups; a study group (n = 22) administered escitalopram 10 mg/day, and a control group (n = 19) administered placebo for a total of 8 weeks before and during the IVF treatment cycle. Patients were assessed at the onset of drug treatment and at embryo transfer. The main outcome measure was the difference in mean score severity rating of depression and anxiety symptoms on the CES-D and Zung questionnaires between groups at the time of embryo transfer. Secondary outcome measures included the MHI rating subscales addressing aspects of psychological distress and coping. At the day of embryo transfer (6 weeks of drug treatment), the CES-D average score for the treatment group was 6.40 (6.71) and 27.47 (4.29) on the Zung Self-Rating Anxiety Scale, while the placebo group scored an average of 15.83 (8.69) and 33.17 (6.95) receptively. These findings were significant (p = .004, p = .015 receptively) and were endorsed by the scoring on the MHI questionnaire subscales. Short-term treatment with SSRI may serve as a prophylactic treatment against the perpetuation and possible worsening of depressive and anxiety symptoms in women undergoing IVF treatments. Further studies concerning pharmacological interventions in larger samples and studies addressing screening for psychological stress indicators in this population are warranted.
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http://dx.doi.org/10.1007/s00737-018-0911-5DOI Listing
August 2019

Gait measures as predictors of poststroke cognitive function: evidence from the TABASCO study.

Stroke 2015 Apr 12;46(4):1077-83. Epub 2015 Feb 12.

From the Stroke Unit and the Center for the Study of Movement, Cognition and Mobility, Department of Neurology, Tel Aviv Medical Center, Tel Aviv, Israel (E.B.A., S.-S.T., E.K., H.H., L.S., E.A., N.G., A. Mike, A.H., A.W., A. Mirelman, N.M.B.); and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel (E.B.A., A.D.K., E.K., H.H., E.A., N.G., N.M.B., J.M.H.).

Background And Purpose: Patients with stroke are at risk for developing cognitive impairment. We tested whether the assessment of balance and gait can enhance the prediction of long-term cognitive outcome in stroke survivors.

Methods: Participants were patients with first-ever, mild-moderate ischemic stroke or transient ischemic attack from the Tel Aviv Brain Acute Stroke Cohort (TABASCO) study, a large prospective cohort study, who underwent 3-T MRI and were followed for ≥2 years using neurological, neuropsychological, and mobility examinations 6, 12, and 24 months after the index event.

Results: Data were available for 298 patients (age: 66.7±9.6 years). Forty-six participants (15.4%) developed cognitive decline (CD) over the 2 years of follow-up. The CD group and cognitively intact group did not differ in their neurological deficits or in their infarct volume or location. Nonetheless, 6 months after stroke, the Timed Up and Go test took longer in those who later developed CD (P<0.001). Additionally, the CD group also had lower Berg Balance Scale scores (P<0.001), slower gait (P<0.001), and fewer correct answers during dual-task walking (P=0.006). Separate analyses of the patients with transient ischemic attack revealed similar results. Multivariate regression analysis showed that Timed Up and Go times >12 s at 6 months after stroke/transient ischemic attack was a significant independent risk marker of CD 24 months after stroke (odds ratio=6.07, 95% confidence interval: 1.36-27.15).

Conclusions: These results suggest that measures of balance and gait are significant risk markers of cognitive status 2 years after stroke. Relatively simple, performance-based tests of mobility may enhance the identification of stroke/transient ischemic attack survivors who have an increased risk of developing CD.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01926691.
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http://dx.doi.org/10.1161/STROKEAHA.114.007346DOI Listing
April 2015