Phase II trial of sequential high-dose chemotherapy with paclitaxel,melphalan and cyclophosphamide,thiotepa and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer

A single high-dose cycle of chemotherapy can produce response rates in excess of 50%. However, disease-free survival (DFS) is 15-20% at 5 years. The single most important predictor of prolonged DFS is achieving a complete response (CR). Increasing the proportion of patients who achieve a complete response may improve disease-free survival. Women with metastatic breast cancer and at least a partial response (PR) to induction chemotherapy received three separate high-dose cycles of chemotherapy with peripheral blood progenitor support and G-CSF. The first intensification was paclitaxel (825 mg/m(2)), the second melphalan (180 mg/m(2)) and the third consisted of cyclophosphamide 6000 mg/m(2) (1500 mg/m(2)/day x 4), thiotepa 500 mg/m(2) (125 mg/m(2)/day x 4) and carboplatin 800 mg/m(2) (200 mg/m(2)/day x 4) (CTCb). Sixty-one women were enrolled and 60 completed all three cycles. Following the paclitaxel infusion most patients developed a reversible, predominantly sensory polyneuropathy. Of the 30 patients with measurable disease, 12 converted to CR, nine converted to a PR*, and five had a further PR, giving an overall response rate of 87%. The toxic death rate was 5%. No patient progressed on study. Thirty percent are progression-free with a median follow-up of 31 months (range 1-43 months) and overall survival is 61%. Three sequential high-dose cycles of chemotherapy are feasible and resulted in a high response rate. The challenge continues to be maintenance of response and provides the opportunity to evaluate strategies for eliminating minimal residual disease.     

Gamete intrafallopian transfer vs superovulation with intrauterine insemination for the treatment of infertility

Superovulation with intrauterine insemination (SO-IUI) has been suggested as an alternative to gamete intrafallopian transfer (GIFT), despite the absence of controlled or comparative trials. We retrospectively analyzed all GIFT and SO-IUI cycles performed concurrently from January 1985 to August of 1987 at a single university center. Pregnancy rates were significantly better for GIFT than SO-IUI (P<0.001), with an odds ratio of 3.25 (P=0.001). Stepwise multiple logistic regression identifield factors that correlate with pregnancy: absence of endometriosis (P=0.05), infertility<3 years' duration (P=0.002), TMS 30×10⁶ (P=0.005), and treatment with GIFT rather than SO-IUI (P=0.001). These data give a first approximation of the increased efficacy of GIFT versus SO-IUI and provide valuable insight into significant confounding variables to be considered when planning a randomized, prospective trial to evaluate these techniques.     

Penetration of zona-free hamster oocytes using human sperm aspirated from the epididymis of men with congenital absence of the vas deferens: comparison with human in vitro fertilization.

OBJECTIVES: To assess the ability of sperm aspirated from the epididymis of men with congenital absence of the vas deferens to penetrate zona-free hamster oocytes. To directly compare the performance of human epididymal sperm in the zona-free hamster oocyte sperm penetration assay (SPA) with the results of human in vitro fertilization (IVF). DESIGN: Sperm penetration assay was carried out with epididymal sperm retrieved microsurgically, and with ejaculated sperm obtained from fertile donors (internal controls). For direct comparison, SPA was performed with the same epididymal sperm sample used for IVF. PATIENTS, PARTICIPANTS: Men with congenital absence of the vas deferens undergoing sperm aspiration as part of their infertility treatment and control donors who provided ejaculated sperm. RESULTS: Epididymal sperm penetrated SPA with a score of 0% to 30%. The SPA scores for internal controls using ejaculated sperm was 30% to 71%. Linear regression analysis of the association between penetration scores in SPA and fertilization rate in IVF indicated a positive correlation that was highly significative. CONCLUSIONS: These findings using SPA confirm previous reports on the fertilizing potential of human epididymal sperm and its ability to produce normal pregnancies. The good correlation between SPA and human IVF using epididymal sperm suggest that SPA is an excellent bioassay to test laboratory experimental conditions for improving fertilizing capacity of human epididymal sperm.     

Results of tubal embryo transfer in premature ovarian failure

The transfer of embryos generated in vitro to the fallopian tubes in 11 cases of premature ovarian failure resulted in 9 clinical pregnancies. This approach may have theoretical advantages over GIFT and IVF-ET in agonadal patients.     

Gamete intrafallopian transfer (GIFT): use of minilaparotomy and an individualized regimen of induction of follicular development

The performance of the gamete intrafallopian transfer (GIFT) technique, utilizing an individualized regimen of follicular induction and minilaparotomy in 45 patients with infertility of varying etiologies is reported. The induction regimen consisted of the administration of clomiphene citrate, 100 mg, from day 3 to day 7, and 150 IU FSH/LH (human menopausal gonadotropin [hMG]) from day 6 on. Human chorionic gonadotropin (hCG; 10,000 IU) was administered when at least two follicles measured 16 mm or more in diameter and when serum estradiol (E2) measurement revealed levels of 350 pg/ml per each main follicle. Up to two oocytes and 100,000 motile sperm were transferred to the fallopian tubes via the fimbria, using a catheter. Of the 45 cases, 13 became pregnant by clinical criteria (29 per cent). Of these 13 pregnancies, nine continued to term (69 per cent), three miscarried spontaneously (12 per cent) and one was an ectopic (7 per cent). Of the nine pregnancies that continued to term, five (55 per cent) were twins. Details of the GIFT procedure as well the preliminary non-human primate research studies that led to the development of the GIFT technique are discussed. It is concluded that GIFT is an excellent alternative to in vitro fertilization and embryo transfer (IVF; ET) in all cases of infertility that failed to conceive using conventional forms of therapy and in which the female partner presents at least one normal fallopian tube.     

Leptomeningeal relapse of multiple myeloma following allogeneic stem cell transplantation

Progressive multiple myeloma may manifest features of 'de-differentiation', including a plasmablastic appearance, failure to secrete paraprotein, extramedullary involvement, and resistance to treatment. A 44-year-old woman with kappa-light chain myeloma underwent allogeneic stem cell transplantation (SCT). Twenty months later she developed paraspinal plasmablastic myeloma in the absence of paraprotein in urine or myeloma in the marrow. The paraspinal masses responded to chemotherapy. At 30 months she developed myelomatous meningitis, which proved resistant to intrathecal chemotherapy, irradiation, and donor lymphocyte infusion (DLI). The leptomeningeal disease led to death at 38 months. This is the first report of leptomeningeal relapse of myeloma after allografting.     

Chances of reversibility in early sensory deprivation of the Homo vulnerabilis: A 5-year (and ongoing) prospective study

Background: This prospective study evaluated the effectiveness of a rehabilitation program in vulnerable children with language deficits.

Aims/Objectives: Evaluating reversibility of a sensory understimulation.

Material/Methods: Two groups of five students, each, (sensory and not sensory deprived) were evaluated at ages 5 and 11. Both groups were taught the compulsory national educational program. The sensory deprived group also had a 5-year rehabilitation program. After that time, their language and vocabulary were reevaluated.

Results: Both groups became able to read, write and perform mathematical operations. Both groups took the compulsory elementary school national performance test and all of them performed above the national average. Despite these good performances the differences between both groups regarding language persisted.

Conclusions: Deficits in children with early sensory deprivation are improved with rehabilitation programs. In order to achieve better restoration, intervention should be done earlier than at 5 years of age. Even if some deficits are not fully reversible, the improvement is significant and allows social inclusion and the possibility of breaking their circle of vulnerability.

Significance: Documenting the importance of early rehabilitation in sensory deficits.     

Multiple gestation as a marker of reproductive efficacy: learning from assisted reproductive technologies

This study postulates that apart from the number of embryos transferred, women with multiple gestation represent a subgroup of highly fertile individuals, whose embryos implant with higher efficiency than women with single gestation. Furthermore, each embryo generated from these women has a higher chance of reaching full term. The objective of this study was to compare implantation rate with the outcome of pregnancy (up to week 20) in multiple gestations following assisted reproductive techniques. The study group comprised 162 women with multiple gestation after assisted reproduction, followed prospectively with at least three ultrasound examinations performed between weeks 5 and 20 after the last menstrual period. Control group A comprised 344 fertile women with spontaneous single pregnancy followed with transvaginal ultrasound. Control group B consisted of 317 infertile women conceiving with single gestation after assisted reproduction and followed prospectively as in the study group. Embryo implantation rate and spontaneous embryo/fetal reduction, either partial or total (abortion), were registered in each case. Overall implantation in women with multiple gestation was higher (54.6%) than in the corresponding controls (25.6%). Furthermore, spontaneous embryo/fetus reduction was similar in the study cases and in fertile women (12.6 and 10.8% respectively) and significantly smaller than in the control group B (20.8%). Women with high reproductive efficacy exposed to assisted reproductive techniques generate cohorts of good quality embryos, with a high chance of implantation and of reaching birth.     

Current advances in the diagnosis and management of intracranial germ cell tumors

Central nervous system (CNS) germ cell tumors (GCT) account for less than 5% of primary brain tumors in children and young adults, but they continue to attract much attention. Over the past decade, two advances have led to re-evaluation of what constitutes conventional therapy for CNS GCT. For pure germinomas, the challenge remains the determination of the optimal field and dose of irradiation and whether or not the use of chemotherapy can lead to a reduced dose or elimination of irradiation altogether without compromising disease control or survival. For non-germinomatous germ cell tumors, an improvement in the current dismal prognosis is imperative.