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Summary:The prognosis of metastatic malignant mesenchymal tumors (MMT) remains poor. Given the chemosensitivity of these neoplasms, a phase II study of high-dose thiotepa (HDT) was performed to evaluate the efficacy of this drug in this particular subset of pediatric tumors. Between 1986 and 1998, 18 patients, previously treated with conventional therapy for metastatic or refractory MMT, entered the study. Thiotepa was administered at a daily dose of 300 mg/m 2 for 3 consecutive days. Hematopoietic stem cell rescue, consisting of bone marrow transplantation or peripheral stem cell transplantation, was performed 2 days after completion of HDT. A response exceeding 50% was observed in 6/18 patients (response rate 33%). Toxicity was severe but never led to death. HDT used at a dose of 900 mg/m 2 yields measurable anti-tumor activity in previously treated patients. The next step in these particularly poor prognosis metastatic MMT will be to investigate HDT combined with other drugs, known to be efficient at high doses. Bone Marrow Transplantation (2000) 26, 627-632. Keywords: thiotepa; BMT; rhabdomyosarcoma; sarcoma; children Metastatic malignant mesenchymal tumors are rare but have a notoriously poor outcome. In stage IV rhabdomyosarcoma (RMS), for example, conventional chemotherapy combined with local treatment yields a cure rate of approximately 20%. As RMS is a chemosensitive tumor, it was thought that high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation could potentially improve the outcome of patients afflicted by these tumors. The dose-effect relationship is essentially effective in chemosensitive malignancies. High-dose thiotepa has yielded significant anti-tumor activity in a variety of pediatric solid tumors. 1,2 The purpose of this phase II study was to evaluate the anti-tumor effect of this molecule in pediatric MMT and to describe its potential role in the future treatment of high-risk MMT in children.

That any anti-androgen effect could be observed on AMH in our CPA group in addition to the gonadotropin-suppressing effect suggests that either androgens are not involved in AMH regulation or that they act by interfering with gonadotropin effects on granulosa cells.

BackgroundPulsatile GnRH therapy is the gold standard treatment for ovulation induction in women having functional hypothalamic amenorrhea (FHA). The use of pulsatile GnRH therapy in FHA patients with polycystic ovarian morphology (PCOM), called “FHA-PCOM”, has been little studied in the literature and results remain contradictory. The aim of this study was to compare the outcomes of pulsatile GnRH therapy for ovulation induction between FHA and “FHA-PCOM” patients in order to search for an eventual impact of PCOM.MethodsRetrospective study from August 2002 to June 2015, including 27 patients with FHA and 40 “FHA-PCOM” patients (85 and 104 initiated cycles, respectively) treated by pulsatile GnRH therapy for induction ovulation.ResultsThe two groups were similar except for markers of PCOM (follicle number per ovary, serum Anti-Müllerian Hormone level and ovarian area), which were significantly higher in patients with “FHA-PCOM”. There was no significant difference between the groups concerning the ovarian response: with equivalent doses of GnRH, both groups had similar ovulation (80.8 vs 77.7 %, NS) and excessive response rates (12.5 vs 10.6 %, NS). There was no significant difference in on-going pregnancy rates (26.9 vs 20 % per initiated cycle, NS), as well as in miscarriage, multiple pregnancy or biochemical pregnancy rates.ConclusionPulsatile GnRH seems to be a successful and safe method for ovulation induction in “FHA-PCOM” patients. If results were confirmed by prospective studies, GnRH therapy could therefore become a first-line treatment for this specific population, just as it is for women with FHA without PCOM.

In our study, GnRH therapy was more successful and safer than gonadotropins, for ovulation induction in "FHA-PCOM" patients. If results were confirmed by prospective studies, it could become a first-line treatment for this population, just as it is for FHA women without PCOM.