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Desvignes F.,Pole de Gynecologie obstetrique Reproduction Humaine | Pouly J.L.,Pole de Gynecologie obstetrique Reproduction Humaine | Janny L.,Laboratoire AMP | Canis M.,Pole de Gynecologie obstetrique Reproduction Humaine | And 4 more authors.
Gynecologie Obstetrique Fertilite | Year: 2014

Objectives Ovarian Tissue Cryopreservation (OTC) is a very promising approach of fertility preservation for women and young patients who have to follow gonadotoxic treatments (chemotherapy, radiotherapy...). The aim of this study was to analyse the indications and the outcomes of the patients who had OTC in our center during the last 17 years. Patients and methods The study is retrospective. Forty-six patients, who underwent OTC in the Laboratory of Reproductive Biology of the University Hospital of Clermont-Ferrand, between January 1997 and December 2009, were included. Results The average age on the day of ovarian tissue harvesting was 19.5 years. Fifty-two percent of the patients were minor. In order of decreasing frequency, the diseases for which OTC has been proposed were hematologic, ovarian tumors, sarcoma ou PNET and breast neoplasia. In 93.5 %, the harvesting of ovarian cortex was performed by laparoscopy. After OTC, 82.6 % of the patients were treated by chemotherapy. A bone marrow transplant was performed for 48 % of the study patients. At the time of data collection, 57 % of the patients who had evaluation of their ovarian function presented premature ovarian failure. Eight patients had one or more pregnancies after treatment. It was a natural pregnancy for five of them. The three others were obtained by medically assisted procreation (in vitro fertilization and oocyte donation). Discussion and conclusion We report a long-term follow-up of patients treated in our center for OTC. The originality of our study is to evaluate all aspects of OTC from the decision to propose the patients an OTC to their outcomes several years after the ovarian tissue harvesting. It is therefore a multidisciplinary approach both oncology, gynecological and pediatric whereas OTC is often considered restrictively in the literature. Finally, it seems to be essential to establish a specific medical care for these patients. This monitoring will allow an adequate assessment of pubertal development and ovarian function, management of estrogen deficiency and secondary infertility, supporting patients in their desire for motherhood. © 2014 Elsevier Masson SAS. All rights reserved.

Merlin E.,Center Regional Of Cancerologie Et Therapie Cellulaire Pediatrique | Merlin E.,French Institute of Health and Medical Research | Goncalves-Mendes N.,Center Regional Of Cancerologie Et Therapie Cellulaire Pediatrique | Hannani D.,French Institute of Health and Medical Research | And 9 more authors.
Transplant Immunology | Year: 2011

The benefits of extracorporeal photochemotherapy (ECP; psoralen and UVA exposure of blood mononuclear cells) in graft-versus-host-disease (GVHD) are well-recognized, but the mechanisms of action remain elusive. As the metabolism of l-arginine in immune cells is known to play a role in immune tolerance, we investigated the effect of ECP on arginine metabolism, and the influence of extracellular l -arginine concentration on the response to ECP in cells from patients on therapy by ECP for a GVHD and healthy donors cultured before and after ECP in the presence of different concentrations of arginine (0, 50, 100, 200 and 1000 μmol/l). At baseline arginine was not metabolized through the same pathway in patients and donors. When cells were exposed to ECP, the production of ornithine but not NO° was enhanced, while mRNA of arginase 1 was up-regulated but not INOS. In GVHD patients, increasing arginine concentration resulted in down-regulation of IFNγ and TNFα mRNA expression, whereas IL10 was up-regulated especially at physiological plasma levels (between 0 and 100 μM). Overall, our study shows that ECP orients the metabolism of arginine toward the arginase pathway together with shifting the cytokine profile toward IL-10, providing new insights into the enigmatic mechanism of action of ECP. © 2010 Elsevier B.V.

Paillard C.,Center Regional Of Cancerologie Et Therapie Cellulaire Pediatrique | Rochette E.,Center Regional Of Cancerologie Et Therapie Cellulaire Pediatrique | Rochette E.,French Institute of Health and Medical Research | Lutz P.,Service de Pediatrie i | And 23 more authors.
Bone Marrow Transplantation | Year: 2013

We report French prospective experience with reduced-intensity conditioning-allo-SCT in 46 patients (median age: 15.5 years, 4.8-20.2) presenting high-risk AL (n=11), Hodgkin's lymphoma (n=15) or solid tumors (n=20). Graft sources were BM (n=21), PBSC (n=20) and cord blood (CB; n=5) from related (n=20) or unrelated (n=26) donors. For CB grafts, only one patient out of five achieved sustained engraftment. For PBSC/BM grafts, engraftment rate was 95%, hematopoietic recovery times were not significantly different between BM, PBSC, sibling or unrelated grafts, day+100. Full donor chimerism was achieved in 94% of patients, and incidences of primary acute GVHD and chronic GVHD were 49% and 14%, respectively. Underlying disease was fatal in 39% of patients. TRM was 6.9%. Three-year OS was 49.15%. OS and EFS were not significantly different between patients transplanted with different grafts and with or without primary GVHD. Patients with solid tumor or measurable disease at transplant had poorer outcomes. Three-year EFS: 33.3% for ALL, 75.0% for AML, 51.8% for Hodgkin's lymphoma, 28.6% for neuroblastoma and 22.2% for sarcoma patients. This multicentre study concluded that Bu/fludarabine/anti-thymocyte globulin conditioning with PB or BM, related or unrelated grafts in patients with various malignancies at high-risk for transplantation toxicity results in high engraftment rates, low TRM and acceptable survival.

Merlin E.,Center Regional Of Cancerologie Et Therapie Cellulaire Pediatrique | Merlin E.,French Institute of Health and Medical Research | Kanold J.,Center Regional Of Cancerologie Et Therapie Cellulaire Pediatrique | Kanold J.,French Institute of Health and Medical Research | And 2 more authors.
Expert Opinion on Biological Therapy | Year: 2012

Extracorporeal photochemotherapy has been used for almost three decades for the treatment of several T-cell-mediated diseases, and its efficacy has been proven in few well-designed controlled randomized trials. However, to date, there are no reliable data on a hypothetic dose-effect, optimal rhythm of administration, drug interactions, or the "pharmacokinetics" and "pharmacodynamics" of this cell therapy. In particular, it is not clear whether ECP gains to be used in combination with immunosuppressive or immunomodulative drugs. In the future, clinical trials may address these issues in order to clarify the most beneficial use of a cell therapy which absence of toxicity is uniformly recognized. © 2012 Informa UK, Ltd.

Chambon F.,Center Regional Of Cancerologie Et Therapie Cellulaire Pediatrique | Chambon F.,French Institute of Health and Medical Research | Chambon F.,Clermont University | Brugnon F.,Assistance Medicale A La Procreation | And 10 more authors.
Human Fertility | Year: 2016

Abstract: Significantly improved survival rates in children and adolescents with cancer have put fertility preservation high on the pediatric oncology agenda. Here we report a retrospective single-center study of 13 years experience of ovarian tissue cryopreservation (OTC) before sterilizing treatment in order to define the safety/benefits of OTC and study clinical/hormonal outcomes in girls. From 2000 to 2013, OTC was performed in 36 girls: eight had non-malignant disease and 28 had malignant disease. Laparoscopy was used to collect a third of each ovary that was frozen by a slow cooling protocol. Indications for OTC were 13 auto-, 19 allo-stem-cell-transplantation and 4 sterilizing chemotherapy. Ovarian tissue harvested by intraumbilical laparoscopy led to no major postoperative complications and did not delay chemotherapy. Histological analysis of ovarian tissue showed an average of 9 primordial follicles/mm2 [0–83] and no malignant cells were identified. Median post-harvest follow-up was 36 months [1–112]: 26 girls were alive in complete remission and 10 had died. Hormonal results were evaluable for 27 patients (median age 17 yrs [5–26]): 16 patients were in premature ovarian insufficiency. OTC sampling one third of each ovary appears to be an appropriate approach to preserve fertility in children without consequences on subsequent therapeutic program. © 2016 The British Fertility Society.

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