scholarly journals Changing the Natural History of Fanconi Anemia Complementation Group-À with Gene Therapy: Early Results of U.S. Phase I Study of Lentiviral-Mediated Ex-Vivo FANCA Gene Insertion in Human Stem and Progenitor Cells

2020 ◽  
Vol 26 (3) ◽  
pp. S39-S40
Author(s):  
Agnieszka Czechowicz ◽  
Paula Rio ◽  
Juan E. Bueren ◽  
Brian Beard ◽  
Eileen Nicoletti ◽  
...  
2013 ◽  
pp. 150127063140004
Author(s):  
Wei-Li Di ◽  
Jemima E Mellerio ◽  
Catina Bernadis ◽  
John Harper ◽  
Alya Abdul-Wahab ◽  
...  

1979 ◽  
Vol 27 (10) ◽  
pp. 1395-1397 ◽  
Author(s):  
A M Landolt

Immunohistochemistry and electron microscopy allow new insights into the biology and natural history of the proliferative processes of the hypophysis. Hyperplasia can be diffuse or focal. Its function and/or growth are controlled by hypothalamic factors. Hyperplasia may precede the formation of an adenoma. Function and/or growth of adenomas is partially or completely independent of hypothalamic regulation. Adenomas are divided according to their functional activity into an endocrine active and inactive group. A further subdivision is made according to the secreted hormone. Inactive adenomas may have lost the ability to produce hormones, may secrete hormones at a very low rate, or may secrete abnormal substances.


2021 ◽  
Author(s):  
Francesca Tucci ◽  
Stefania Galimberti ◽  
Luigi Naldini ◽  
Maria G Valsecchi ◽  
Alessandro Aiuti

Abstract To provide an assessment of the safety of ex-vivo gene therapy (GT) with hematopoietic stem and progenitor cells (HSPC), we reviewed in a systematic manner the literature on monogenic diseases to describe survival, genotoxicity and engraftment of gene corrected HSPC, across vector platforms and diseases. From 1995 to 2020, 55 trials for 14 diseases met inclusion criteria and 406 patients with primary immunodeficiencies (55.2%), metabolic diseases (17.0%), haemoglobinopathies (24.4%) and bone marrow failures (3.4%) were treated with gammaretroviral vector (γRV) (29.1%), self-inactivating γRV (2.2%) or lentiviral vectors (LV) (68.7%). The pooled overall incidence rate of death was 0.9 per 100 person-years of observation (PYO) (95%CI = 0.37–2.17). There were 21 genotoxic events out of 1504.02 PYO. All these events occurred in γRV trials (0.99 events per 100 PYO, 95%CI = 0.18–5.43) for primary immunodeficiencies. Pooled rate of engraftment was 86.1% (95%CI = 66.9–95.0%) for γRV and 99.0% (95%CI = 95.1–99.8%) for LV HSPC-GT (p = 0.002). A comprehensive meta-analysis on HSPC-GT showed stable reconstitution of haematopoiesis in most recipients with superior engraftment and safer profile in patients receiving LV-transduced HSPC.


2020 ◽  
Vol 4 (22) ◽  
pp. 5858-5862
Author(s):  
Caron A. Jacobson ◽  
Marcela V. Maus

Abstract Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 has transformed the natural history of relapsed and refractory B-cell acute lymphoblastic leukemia and aggressive B-cell non-Hodgkin lymphoma. Based on these results, CD19 CAR T cells have since been tested in largely incurable lymphomas, including mantle cell lymphoma, follicular lymphoma, and marginal zone lymphoma, with promising early results that raise the question of whether this cellular immunotherapy could have curative potential and change the natural history of these diseases. This article reviews these results and this hypothesis.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e23150-e23150
Author(s):  
Nikolaos Tsoukalas ◽  
Alexandros Bokas ◽  
Evangelos Bournakis ◽  
Athina Christopoulou ◽  
Christos Papandreou ◽  
...  

e23150 Background: Cancer is associated with thrombosis due to different pathophysiological processes. CAT is the 2nd cause of death in oncology patients and can occur anytime during the natural history of cancer. CAT is not rare complication, can delay anti-cancer therapy and increase health systems costs. Methods: A prospective observational study (Greek Management of Thrombosis-GMaT) conducted by HeSMO in Greek Oncology units for two years aiming to record clinical practice of CAT management. Patients with active cancer who received CAT treatment or thromboprophylaxis were enrolled after signing informed consent. Results: 546 patients were enrolled from 18 oncology units. Primary cancers were: lung 23.9%, pancreas 13.3%, breast 7.6%, colorectal 8.9%, stomach 8.3%, ovarian 7.6% and other 30.5%. 120 patients received LMWH for Venus Thombo-Embolism (VTE) treatment (Group A) and 426 for thromboprophylaxis (Group B). Group A: 89/120 (74.17%) patients continued in 2nd year and 58.6% received CAT treatment (6.9±4.4 months). Only 2 had VTE recurrence in 2nd year (versus 3 in 1st year). 4/120 (3.33%) had bleeding events (grade 1) in 1st year while no bleeding events occurred in 2nd year. Group B: 345/426 (80.98%) patients continued in 2nd year. 126 (30%) had Khorana score ≥3 and 300 (70%) had Khorana score ≤2. In 2nd year, 123 (35.65%) received thromboprophylaxis (7.3±3.7 months) while 79.4% of them were initially treated with High Thrombotic Treatment Agents (HTTA: e.g. platinum, 5-FU) and 83.1% had metastatic disease. In 2nd year, 52.5% received LMWHs at prophylactic dose and 47.5% at therapeutic dose. Overall, 12 (2.82%) had thrombotic events whereas 4 were recorded in 2nd year. Notably, patients treated with therapeutic doses had lower probability to have a thrombotic event (OR: 5.8, 95% CI: 1.7 to 20.5, p < .05). Six (1.41%) bleeding events (grade 1) occurred in 1st year and one (0.81%) in 2nd year. Conclusions: LMWHs can be used for long term CAT management. Therapeutic LMWHs doses as thromboprophylaxis are safe and effective. Khorana score is a useful model for CAT risk assessment but some other factors such as disease stage and HTTA might be taken into account. CAT can occur anytime during the natural history of cancer. Oncologists should be aware about CAT and its negative influences in patients’ prognosis and quality of life.


1991 ◽  
Vol 27 (11) ◽  
pp. 1411-1416 ◽  
Author(s):  
Steven A. Narod ◽  
D.W. Thompson ◽  
M. Jain ◽  
Claus Wall ◽  
Lois M. Green ◽  
...  

Haematologica ◽  
2018 ◽  
Vol 103 (11) ◽  
pp. 1806-1814 ◽  
Author(s):  
Jennifer E. Adair ◽  
Devikha Chandrasekaran ◽  
Gabriella Sghia-Hughes ◽  
Kevin G. Haworth ◽  
Ann E. Woolfrey ◽  
...  

2003 ◽  
Vol 13 (4) ◽  
pp. 215-219
Author(s):  
N. De Roeck ◽  
A. Hashemi-Nejad

Acetabular dysplasia may present as previously undiagnosed or as a sequel to treated DDH in a young adult, with a natural history of subsequent development of early osteoarthritis. Patients with acetabular dysplasia, a normal neck shaft angle, no significant leg length inequality and who demonstrate congruency at arthrogram are considered suitable for realignment pelvic osteotomy. We report the results of 15 young adults who underwent a modified Tonnis triple osteotomy with a mean 22-month follow-up. The modification was that the ischial osteotomy was performed through a groin incision. The only common complication was the requirement of catheterisation post-operatively (60%). There were no infections. There was one delayed union but no non-unions. One patient developed a deep vein thrombosis. All patients reported an improvement in their symptoms and level of activity, with a mean post-operative Harris hip score of 92. All showed an improved centre-edge angle of 28° (mean increase of 18°) and acetabular angle of 37° (mean decrease of 13°). The early results of this procedure show it to be a safe and useful option to delay the natural history of early osteoarthritis in the young adult.


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