Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Only limited data is currently available on long-term gonadal toxicity and its impact on bone mineralization in men and women treated for Hodgkin's disease. The present study was therefore conducted to evaluate gonadal toxicity and bone loss in 49 patients with Hodgkin's disease 2-10 (median 5.37) years after chemotherapy. Most patients were treated with the COPP/ABVD regimen +/- irradiation according to the protocols of the German Hodgkin Study Group. Blood samples were tested for gonadotropins (FSH, LH), gonadal steroids, parathyroid hormone, osteocalcin, and calcitonin. Bone mineral density was measured using single- and dual-energy quantitative computed tomography as well as single-photon absorptiometry. FSH serum levels were significantly increased in 21/27 (80%) men demonstrating germ-cell aplasia. 13/15 (86%) men showed azoospermia after the COPP/ABVD regimen. In contrast, testosterone levels were within normal limits in all men tested, suggesting normal Leydig-cell function. 17/22 (77%) women exhibited increased FSH and LH levels, indicating premature ovarian failure. Women with therapy-induced ovarian failure had a significantly lower trabecular (98 +/- 34) and cortical (292 +/- 48 mg/cm3) spinal bone density than those with normal ovarian function. Men showed no evidence of bone loss after therapy. These data suggest severe gonadal toxicity in both men and women treated with the COPP/ABVD regimen. In female patients, drug-induced ovarian failure has a significant impact on bone mineralization.
 ...
PMID:Long-term gonadal dysfunction and its impact on bone mineralization in patients following COPP/ABVD chemotherapy for Hodgkin's disease. 128 Apr 63

Between October 10, 1981 and December 31, 1987, we used the Hodgkin POF 81/12 protocol to treat 235 patients aged from 5 to 65 years (mean 30 years) with localized Hodgkin's disease clinically classified as stage IA (n = 6), stage IIA (n = 128) and stage IIB (n = 53). A contiguous lesion was present in 22 cases and a mediastinal lesion in 170 cases. The patients received 3 monthly courses of ABVD-MP (doxorubicin 25, bleomycin 10, vinblastine 6, dacarbazine 375 and methylprednisolone 120 mg per sq.m intravenously on days 1 and 15), except for stage IA non-mediastinal patients who received only one course. Thereafter, in the absence of failure (lack of changes or progression under chemotherapy), a 40 Gy wide focal irradiation and a 30 Gy prophylactic lumbo-splenic irradiation were performed. Complete remission (CR) was obtained in 229 patients, and the 6 failures (4 after ABVD-MP, 2 after radiotherapy) were treated with specific programmes. On December 1, 1988 (median survival 42 months, range 12-86 months) we had recorded 9 relapses (after 9 to 51 months) and 7 deaths (2 failures, 2 relapses and 3 patients in CR: ovarian carcinoma, road accident, exploratory pleural puncture). The current actuarial relapse and survival rates at 7 years are 5 and 94 respectively. Two unfavourable forms of the disease were identified: infra-diaphragmatic with massive lumbo-aortic lesions (5 cases: 1 failure, 1 relapse) and supra-diaphragmatic with a mediastinum/chest ratio of 0,45 or more (30 cases: 5 failures, 5 relapses). In the 200 patients devoid of these 2 risk factors the results obtained were: CR 100 percent, only 2 relapses and survival at 7 years 98 percent.
 ...
PMID:[Treatment of localized forms of Hodgkin's disease with 3 courses of chemotherapy (ABVD-MP) in combination with wide focal and prophylactic lumbo-splenic radiotherapy. The POF 81/12 protocol]. 248 May 92

Ovarian function has been studied in 44 adult females who previously received quadruple chemotherapy (MVPP) for Hodgkin's disease. The median age at treatment was 23 years, and the length of time between completion of treatment and study ranged from 6 months to 10 years (median, 30 months). Seventeen women maintained regular menses, 10 developed oligomenorrhea, and 17 developed amenorrhea. At treatment, the 17 women who subsequently developed amenorrhea were significantly older (median, 30 years) than those who maintained regular menses (median, 22 years) or developed oligomenorrhea (median, 23 years). All patients older than 36 years at the start of treatment stopped menstruating during chemotherapy. The cause of the menstrual disturbance in these patients was chemotherapy-induced ovarian damage characterized by high serum gonadotrophin and low serum estradiol concentrations. After completion of treatment there were 17 pregnancies, which resulted in 9 normal infants, 3 terminations, and 4 spontaneous abortions. Nine patients took the combination oral contraceptive pill throughout chemotherapy; however, subsequently 4 developed amenorrhea and 3 oligomenorrhea, suggesting that these patients had not been protected from chemotherapy-induced ovarian damage. Estrogen replacement therapy was of definite benefit in the symptomatic patients with premature ovarian failure.
 ...
PMID:The effect of combination chemotherapy on ovarian function in women treated for Hodgkin's disease. 641 21

With the increasing cure rate of patients treated for Hodgkin's and non-Hodgkin's lymphoma, the evaluation of late effects on gonadal function remains an important issue. The gonadal function of relapse-free long-term survivors with high-grade non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) were studied; 24 of 119 patients with NHL treated between 1980 and 1990 and 66 of 364 patients with HD treated between 1975 and 1990 at Hannover University Medical School, who were younger than 45 years of age and in complete remission at the time of evaluation for at least 24 months after completion of therapy, were included into the analysis. Of 24 patients with NHL, 1/10 women (10%) and only 3/14 men (21%) showed signs of gonadal dysfunction. Three of these four patients had been treated with combined modality therapy followed by maintenance COP chemotherapy, resulting in high cumulative doses of cyclophosphamide (range: 12-43 g). In comparison, 13/26 (50%) women with HD suffered from premature ovarian failure, and 26/40 (65%) men showed signs of gonadal dysfunction with significant FSH elevations. No significant difference in the incidence of gonadal toxicity existed in patients treated with combined modality who received irradiation to either supra- or infradiaphragmatic radiation fields in combination with chemotherapy (70% versus 62%). A comparison of the chemotherapy regimens used in patients with NHL or HD shows that patients from both groups had received comparable median cumulative doses of cyclophosphamide, vincristine, and adriamycin, but only patients with HD had additionally received a median cumulative dose of 13.3 g of procarbazine per patient. A tendency towards a higher incidence of gonadal toxicity with higher cumulative doses of procarbazine received was found in patients with HD. The frequency of gonadal dysfunctions is markedly lower in patients treated for non-Hodgkin's lymphoma than in patients treated for Hodgkin's disease, approximately half of whom will be affected by long-term gonadal toxicity. Although the use of more intensive radiotherapy in patients with HD compared with NHL patients makes the evaluation of the influence of radiotherapy on gonadal toxicity more difficult, the current retrospective analysis raises the concern that, in addition to infradiaphragmatic radiotherapy, the use of procarbazine in regimens for the treatment of HD, like COPP or MOPP, may be a possible explanation for the differences in gonadal toxicity observed between patients with HD and those with NHL. Regimens including procarbazine should be avoided in patients wanting to preserve fertility since alternative chemotherapies with at least equal efficacy are available.
 ...
PMID:Long-term gonadal toxicity after therapy for Hodgkin's and non-Hodgkin's lymphoma. 816 75

To examine whether the concomitant administration of a gonadotrophin-releasing hormone agonist (GnRHa) during combination chemotherapy to young women with lymphoma may facilitate preservation of gonadal function, a prospective clinical protocol was undertaken in 18 cycling women with lymphoma, aged 15-40 years. Thirteen patients suffered from Hodgkin disease (HD) and 5 from non-Hodgkin lymphoma. After informed consent a monthly injection of depot D-TRP6-GnRHa was administered for a maximum of 6 months starting prior to chemotherapy. Most of these patients (15/18) were treated with the MOPP/ABV(D) combination chemotherapy followed by mantle field irradiation in 10 patients. Hormonal profile [luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol, testosterone, progesterone, insulin-like growth factor (IGF)-1, prolactin] was taken before the GnRHa/chemotherapy co-treatment, and monthly thereafter until resuming spontaneous ovulation and menses. This group of prospectively treated lymphoma patients was compared to a matched control group of 18 women (aged 17-40 years) who have been treated with chemotherapy, mostly MOPP/ABV (14/18), with (11) or without (7) mantle field radiotherapy. Fourteen had Hodgkin's and four non-Hodgkin's lymphoma. Gonadal function was determined clinically, hormonally (LH, FSH, oestradiol, progesterone), and sonographically. Two of the patients in each group died from refractory disease. Of the remaining 16 patients, 15 (93.7%) resumed spontaneous ovulation and menses within 3-8 months of termination of the combined chemotherapy/GnRHa co-treatment. In contrast, only seven (39%) of the 18 similarly treated patients in the control group (chemotherapy without GnRHa) resumed ovarian cyclic activity (regular menses). The other 11 experienced premature ovarian failure (POF) (61%). Out preliminary data suggest a possible significant protective effect of GnRHa co-treatment with chemotherapy from irreversible ovarian damage (POF).
 ...
PMID:Prevention of irreversible chemotherapy-induced ovarian damage in young women with lymphoma by a gonadotrophin-releasing hormone agonist in parallel to chemotherapy. 892 Nov 4

Infertility represents one of the main remote sequelae of cytotoxic chemotherapy given for various malignant diseases. The impairment of gonadal function after cytotoxic chemotherapy is more frequent in the male than in the female. Because dividing cells are more sensitive to the cytotoxic effects of alkylating agents than are cells at rest, it has been hypothesized that inhibition of the pituitary-gonadal axis by gonadotropin-releasing hormone (GnRH) agonists would render the germinal epithelium less susceptible to the cytotoxic effects of chemotherapy. This hypothesis has not been thoroughly clinically tested until recently, although several investigators have demonstrated that GnRH-agonistic analogues (GnRH-a) inhibit chemotherapy-induced ovarian follicular depletion in the rat and Rhesus monkeys. Based on this rationale, we have undertaken a prospective evaluation to determine whether GnRH-a administration during combination chemotherapy for Hodgkin's and non-Hodgkin's lymphoma could prevent posttreatment ovarian damage in women by inducing a temporary prepubertal hormonal milieu. While over 93% of the surviving patients in the GnRH-a and chemotherapy group resumed spontaneous ovulation and menses, less than 40% of the women in the control group of chemotherapy without the GnRH-a cotreatment resumed normal ovarian cyclic activity. More than 60% of the women experienced premature ovarian failure (POF) in the chemotherapy alone group. Our preliminary results suggest that GnRH-a cotreatment protects against POF during cytotoxic chemotherapy. The GnRH-a and chemotherapy cotreatment may be also suggested for young women treated by cyclophosphamide pulse therapy or other gonadotoxic treatments for systemic lupus erythematosus, organ transplantation and other autoimmune diseases. The technology of cryopreservation of human ova for future fertility in these patients awaits clinical validation and substantiation. This review discusses possibilities to prevent gonadal damage induced by cytotoxic therapy and presents the clinical data currently available.
 ...
PMID:Prevention of gonadal damage during cytotoxic therapy. 924 Jun 25

More than one-half of women treated with pelvic radiation therapy for malignant disease experience premature ovarian failure. Preservation of ovarian function by repositioning the ovaries out of the irradiation field is suggested in all women of reproductive age. This repositioning generally is done by moving the ovaries either medially so they are posterior to the uterus, or laterally so they are in the paracolic gutters. Laparoscopic medial transposition has been reported, with mixed results. A woman underwent successful laparoscopic lateral transposition before irradiation for stage IIIa Hodgkin disease. A review of published cases suggests that this is preferable to medial transposition.
 ...
PMID:Laparoscopic lateral ovarian transposition before radiation treatment of Hodgkin disease. 934 69

High dose chemotherapy and radiotherapy have radically increased long term survival of young cancer patients. Among the side effects of chemotherapy treatments are ovarian failure and infertility, which are of particularly great concern to young cancer patients. Recently, cryopreservation procedures such as in vitro fertilization and embryo storage, or ovarian tissue cryopreservation have been used to preserve fertility in patients subjected to cancer treatments. Knowledge of the risks and probabilities of ovarian failure as well as the risks of the cryopreservation procedures is crucial for patients and physicians in order to make informed choices that will best serve the patients interests. This article presents data of a prospective study that determines the risk of ovarian failure following exposure to chemotherapy as well as a review of related publications. Progressive, dose-related depletion of primordial follicles is noted on histology, explaining the risk of undergoing premature ovarian failure years after exposure to chemotherapy. The safety of ovarian tissue cryopreservation procedures with a new round biopter was evaluated, as well as the risk of malignant cell transmission. It has been shown that laproscopic ovarian biopsy performed with the round biopter is a safe and efficient method for collection of ovarian tissue in cancer patients. In Hodgkin's disease patients' ovarian cortical tissue obtained for cryopreservation does not contain malignant cells. However the risk of cryopreserving and transferring malignant cells should be tested separately for each disease according to the risk of ovarian metastasis and the ability to detect single malignant cells.
 ...
PMID:Ovarian injury and modern options to preserve fertility in female cancer patients treated with high dose radio-chemotherapy for hemato-oncological neoplasias and other cancers. 1019 22

This retrospective study compares high-dose therapy (HDT) with autologous stem cell transplantation and combined-modality treatment (CT) as a first-line therapy for Hodgkin's disease (HD) for patients with both a clinical stage (CS) IV and/or a mediastinal mass > or =0.45 of the thoracic diameter (MM > or =0.45) at diagnosis, and an incomplete response after the first-line chemotherapy. Data on 42 grafted patients (GP) in Nantes Hospital, France and on 108 combined-modality treated patients (CTP) from two protocols of the GOELAMS group, France (POF 81 and H90) was analyzed. Both groups were comparable except for pulmonary disease in excess in the grafted group (P = 0.01). Among GP, 95% were in complete response at the end of first-line treatment and 77% among CTP. Median follow-up was 53 months (range, 7 to 128 months) for GP and 88 months (range, 25 to 181 months) for CTP. The 5-year freedom from progression (FFP) and event-free survival (EFS) rates were better for GP (87% vs 55% for FFP: P = 0.0004 and 81% vs 51% for EFS: P = 0.0004) whereas the overall survival (OS) rates did not differ significantly (85% for GP vs 71% for CTP: P = 0.06). Similar results were obtained for the groups with a response > or =50% after initial chemotherapy: 91% vs 65% for FFP, P = 0.01; 87% vs 61% for EFS, P = 0.02; and 92% vs 77% for OS, P = 0.2; and for the groups with a response <50%: 80% vs 22% for FFP, P = 0.0003; 72% vs 13% for EFS, P = 0.0001; and 76% vs 46% for OS, P = 0.04. This study shows a better control of the disease with HDT.
 ...
PMID:Front-line high-dose therapy with autologous stem cell transplantation for high risk Hodgkin's disease: comparison with combined-modality therapy. 1205 33

Cryopreservation of ovarian tissue has been proposed for storing gametes of young patients at high risk of premature ovarian failure. Autotransplantation has recently provided some promising results and is still the unique option to restore ovarian function from cryopreserved ovarian tissue in humans. In this article, we analyse data from the combined orthotopic and heterotopic transplantation of cryopreserved ovarian tissue that restored the ovarian function and fertility. Orthotopic transplantation of cryopreserved ovarian tissue at ovarian and peritoneal sites, together with a heterotopic transplantation at the abdominal subcutaneous site, was performed to restore the ovarian function of a 29-year-old woman previously treated with bone marrow transplantation (BMT) for Hodgkin's disease. Ovarian reserve markers progressively suppress within values 5 months after the transplantation (basal FSH 5 mUI/ml and inhibin B 119 ng/ml). Follicular development was observed at all transplantation sites but was predominant at the ovarian site. Six natural cycles were fully documented and analysed. The patient became spontaneously pregnant following the sixth cycle, but unfortunately she later miscarried. Combined orthotopic and heterotopic transplantations succeeded in the restoration of normal spontaneous cycles. Furthermore, this spontaneous pregnancy confirmed the efficiency of this procedure for restoring human fertility.
 ...
PMID:Ovarian function and spontaneous pregnancy after combined heterotopic and orthotopic cryopreserved ovarian tissue transplantation in a patient previously treated with bone marrow transplantation: case report. 1658 22


1 2 Next >>