Eighty-five patients with Wegener's granulomatosis were studied for 21 years at the National Institutes of Health. Patients were treated with a protocol consisting of cyclophosphamide, 2 mg/kg body weight d, together with prednisone, 1 mg/kg body weight d, followed by conversion of the prednisone to an alternate-day regimen. Complete remissions were achieved in 79 of 85 patients (93%). The mean duration of remission for living patients was 48.2 (+/- 3.6) months. Twenty-three patients are off all therapy for a mean duration of 35.3 (+/- 6.3) months without therapy. This study provides a prospective experience with Wegener's granulomatosis and shows that long-term remissions can be induced and maintained in an extremely high number of patients by the combination of daily cyclophosphamide and alternate-day prednisone therapy.

Wegener's granulomatosis: Prospective clinical and therapeutic experience with 85 patients for 21 years

Purpose To develop guidance to practicing oncologists about available fertility preservation methods and related issues in people treated for cancer. Methods An expert panel and a writing committee were formed. The questions to be addressed by the guideline were determined, and a systematic review of the literature from 1987 to 2005 was performed, and included a search of online databases and consultation with content experts. Results The literature review found many cohort studies, case series, and case reports, but relatively few randomized or definitive trials examining the success and impact of fertility preservation methods in people with cancer. Fertility preservation methods are used infrequently in people with cancer. Recommendations As part of education and informed consent before cancer therapy, oncologists should address the possibility of infertility with patients treated during their reproductive years and be prepared to discuss possible fertility preservation options or refer appropriate and interested patients to reproductive specialists. Clinician judgment should be employed in the timing of raising this issue, but discussion at the earliest possible opportunity is encouraged. Sperm and embryo cryopreservation are considered standard practice and are widely available; other available fertility preservation methods should be considered investigational and be performed in centers with the necessary expertise.

https://ascopubs.org/doi/pdf/10.1200/jco.2006.06.5888

American Society of Clinical Oncology Recommendations on Fertility Preservation in Cancer Patients

The Ann Arbor classification for describing the stage of Hodgkin's disease at initial presentation has formed the basis upon which treatment is selected and has allowed comparison of results achieved by different investigators for almost two decades. A meeting was convened to review the classification and modify it in the light of experience gained in its use and new techniques for evaluating disease. It was concluded that the structure of the classification be maintained. It was particularly recommended: (1) that computed tomography (CT) be included as a technique for evaluating intrathoracic and infradiaphragmatic lymph nodes; (2) that the criteria for clinical involvement of the spleen and liver be modified to include evidence of focal defects with two imaging techniques and that abnormalities of liver function be ignored; (3) that the suffix 'X' to designate bulky disease (greater than 10 cm maximum dimension) be introduced; and (4) that a new category of response to therapy, unconfirmed/uncertain com...

Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting.

Background and Methods. MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) has been the standard treatment for Hodgkin's disease for almost 20 years. In a randomized, multicenter trial, we compared three regimens of primary systemic therapy for newly diagnosed advanced Hodgkin's disease in Stages IIIA2, IIIB, and IVA or IVB: (1) MOPP alone given for 6 to 8 cycles, (2) MOPP alternating with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) for 12 cycles, and (3) ABVD alone for 6 to 8 cycles. Patients in a first relapse after radiation therapy were eligible. No additional radiation therapy was given. Patients who did not have a complete response or who had a relapse with either MOPP alone or ABVD alone were switched to the opposite regimen. Results. Of 361 eligible patients, 123 received MOPP, 123 received MOPP alternating with ABVD, and 115 received ABVD alone. The patients were stratified according to age, stage, previous radiation, histologic features, and performance st...

https://www.nejm.org/doi/pdf/10.1056/NEJM199211193272102

Chemotherapy of Advanced Hodgkin's Disease with MOPP, ABVD, or MOPP Alternating with ABVD

Sperm DNA integrity is essential for the accurate transmission of genetic information. It has a highly compact and complex structure and is capable of decondensation-features that must be present in order for a spermatozoon to be considered fertile. Any form of sperm chromatin abnormalities or DNA damage may result in male infertility. In support of this conclusion, it was reported that in-vivo fecundity decreases progressively when > 30% of the spermatozoa are identified as having DNA damage. Several methods are used to assess sperm chromatin/DNA, which is considered an independent measure of sperm quality that may yield better diagnostic and prognostic approaches than standard sperm parameters (concentration, motility and morphology). The clinical significance of this assessment lies in its association not only with natural conception rates, but also with assisted reproduction success rates. Also, it has a serious impact on the offspring and is highly prognostic in the assessment of fertility in cancer patients. Therefore, screening for sperm DNA damage may provide useful information in cases of male idiopathic infertility and in those men pursuing assisted reproduction. Treatment should include methods for prevention of sperm DNA damage.

/pdf/role-of-sperm-chromatin-abnormalities-and-dna-damage-in-male-5a2riixlg7.pdf

Role of sperm chromatin abnormalities and DNA damage in male infertility

Forty-one women with advanced Hodgkin's disease were studied to determine the effect of combination chemotherapy on fertility and ovarian function. Histories and pretreatment ovarian biopsy specimens indicated normal fertility before therapy, thus implying no adverse effect of Hodgkin's disease on female gonadal function. Ovarian activity was assessed after therapy by menstrual history, serial basal body temperatures, and hormonal levels. Each case was assigned to one of three categories: primary ovarian failure (failed ovary), irregular ovarian activity (failing ovary), and normal cyclic ovarian activity (functioning ovary). After therapy, 20 of 41 patients (49%) were categorized as failed, 14 (34%) as failing, and only 7 (17%) as functioning. In 16 months of further observation, progressive loss of ovarian function occurred that was clearly age related but not statistically dose related. Induction of premature, irreversible menopause presents a need for effective hormonal replacement and patient counseling. ( JAMA 242:1877-1881, 1979)

https://jamanetwork.com/journals/JAMA/articlepdf/367065/jama_242_17_020.pdf

Cytotoxic-induced ovarian failure in women with Hodgkin's disease. I. Hormone function.

CYCLICAL COMBINATION CHEMOTHERAPY AND GONADAL FUNCTION: Retrospective Study in Males

Forty-seven men (median age, 31.5 years) were studied prospectively to assess the effect of Hodgkin's disease and subsequent chemotherapy on gonadal function. Before therapy, 16 (43%) of 37 men were functionally subfertile, as assessed by impotence (four of 37) and "inadequate" sperm counts (12 of 37). Histological abnormalities were noted in eight of nine pretreatment testicular biopsy specimens. Additionally, changes were noted in blood hormone levels and libido. After completion of only two cycles of chemotherapy, 14 of 14 men became persistently azoospermic, with blood follicle-stimulating hormone levels four to five times normal. Posttreatment testicular biopsy specimens confirmed germ cell aplasia. During therapy 17 (81%) of 21 men had mild or no libido; irritability in 16 (84%) of 19 and violence in four (18%) of 22 caused additional family distress. While it is clear that cytotoxic therapy induces infertility, these data further indicate that a proportion of men have gonadal dysfunction prior to treatment. ( JAMA 1981;245:1323-1328)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=jama&articleId=374370&pdfFileName=jama_245_13_020.pdf

Male gonadal dysfunction in Hodgkin's disease. A prospective study.

Protection of ovarian function by oral contraceptives in women receiving chemotherapy for Hodgkin's disease

Sixty-six untreated patients with advanced non-Hodgkin's lymphoma of favourable histological type were allocated alternately to initial treatment with cyclophosphamide, vincristine, and prednisolone or with chlorambucil. The complete remission rate was higher in the group receiving combination chemotherapy, but the overall response rate was the same for both groups. The mean duration of complete remission was the same as that of good partial remission, and was the same for both treatments. The duration of remission was influenced by histological type and extent of disease at presentation, but not age. Those who responded to the initial treatment (whether with complete or with good partial remission) survived significantly longer than did non-responders. It is concluded that neither treatment is satisfactory and that new treatment programmes are needed for patients with a favourable prognosis, especially young patients with extensive disease.

S.B. Sutcliffe

Papers

Cytotoxic-induced ovarian failure in women with Hodgkin's disease. I. Hormone function.

CYCLICAL COMBINATION CHEMOTHERAPY AND GONADAL FUNCTION: Retrospective Study in Males

Male gonadal dysfunction in Hodgkin's disease. A prospective study.

Protection of ovarian function by oral contraceptives in women receiving chemotherapy for Hodgkin's disease

Comparison of combined and single-agent chemotherapy in non-Hodgkin's lymphoma of favourable histological type.