A randomized phase III study of carfilzomib vs low-dose corticosteroids with optional cyclophosphamide in relapsed and refractory multiple myeloma (FOCUS).

This randomized, phase III, open-label, multicenter study compared carfilzomib monotherapy against low-dose corticosteroids and optional cyclophosphamide in relapsed and refractory multiple myeloma (RRMM). Relapsed and refractory multiple myeloma patients were randomized (1:1) to receive carfilzomib (10-min intravenous infusion; 20 mg/m2 on days 1 and 2 of cycle 1; 27 mg/m2 thereafter) or a control regimen of low-dose corticosteroids (84 mg of dexamethasone or equivalent corticosteroid) with optional cyclophosphamide (1400 mg) for 28-day cycles. The primary endpoint was overall survival (OS). Three-hundred and fifteen patients were randomized to carfilzomib (n=157) or control (n=158). Both groups had a median of five prior regimens. In the control group, 95% of patients received cyclophosphamide. Median OS was 10.2 (95% confidence interval (CI) 8.4-14.4) vs 10.0 months (95% CI 7.7-12.0) with carfilzomib vs control (hazard ratio=0.975; 95% CI 0.760-1.249; P=0.4172). Progression-free survival was similar between groups; overall response rate was higher with carfilzomib (19.1 vs 11.4%). The most common grade ⩾3 adverse events were anemia (25.5 vs 30.7%), thrombocytopenia (24.2 vs 22.2%) and neutropenia (7.6 vs 12.4%) with carfilzomib vs control. Median OS for single-agent carfilzomib was similar to that for an active doublet control regimen in heavily pretreated RRMM patients.

Kallmann syndrome in three unrelated women and an association with femur-fibula-ulna dysostosis in one case.

We describe three unrelated women with hypogonadotropic hypogonadism and anosmia; that is, Kallmann syndrome. Absence of olfactory bulbs and tracts and different degrees of asymmetric dysplasia of olfactory sulci were demonstrated by MRI. Both the father of Case 1 and the maternal aunt of Case 3 had anosmia, thus autosomal dominant inheritance seems to be likely. Patient 2 had Kallmann syndrome and FFU (femurfibula-ulna) dysostosis as a sporadic occurrence in her family.

[Genetic evaluation of male homosexuality]. / A férfi homoszexuálisok genetikai értékelése.

The family trees of 16 homosexual males are evaluated in the material of their Genetic Counselling Clinic. The familial cluster of three cases corresponded to the X-linked recessive inheritance. The results of family, twin and adoption studies are reviewed and the recent findings of molecular genetic and brain researches are summarised. Male homosexuality comprises of different subgroups, but one major entity is caused by X-linked recessive gene(s). This genetic background represent a predisposition which is triggered or suppressed by external factors.

The Hungarian periconceptional service as a model for community genetics.

OBJECTIVES: This review describes the methods and results of the Hungarian periconceptional service consisting of counselling, examinations and medical interventions. (The term periconceptional is used instead of preconceptional because the early postconceptional period is also involved to this service.) METHODS: The service was based on three steps: check-up examination of reproductive health (i.e., preconceptional screenings), a 3-month preparation for conception, dispensed and/or supervised by qualified nurses, and a better protection in early pregnancy for the most sensitive early development of the embryo for voluntary and eligible couples. RESULTS: Experiences from the coordinating centre of the Hungarian periconceptional service are summarized between February 1, 1984, and January 31, 1999, thus 15 years. Participants with positive family histories, case histories and subjects with genito-urinary infections had a more effective flow towards secondary care. Infertile couples were diagnosed and treated sooner. The periconceptional service is effective for the introduction of periconceptional folic acid-containing multivitamin supplementation and for the reduction of smoking and alcohol consumption in females in the preconceptional period. The rate of major congenital abnormalities (20.6 per 1,000) was significantly lower than expected. CONCLUSIONS: The periconceptional service is feasible and has many benefits. Thus, proper preparation for conception is the earliest and probably the most important effort to prevent genetic diseases.

[Therapeutic importance of the diagnosis of Kallmann syndrome]. / A Kallmann-kór kórismézésének terápiás jelentósége.

Hyposmia with hypogonadotropic hypogonadism was diagnosed as Kallmann syndrome in a 24 years old dizygotic female twin. This syndrome indicates the importance of smell in the sexual development through the progenitor cells in the olfactory placode because luteinizing-hormone-releasing hormone (LHRH) secreting cells of hypothalamus arise from these cells. In addition, substitution therapy may be successful in the treatment of the lack of secondary sex traits and primary amenorrhoea as the presented case demonstrated.