Cyclical Combination Chemotherapy and Gonadal Function

Chapman, RamonaM.; Rees, Linford; Sutcliffe, Simon; Edwards, C. R. W.; Malpas, J. S.

doi:10.1016/s0140-6736(79)90701-3

Cited by 238 publications

(93 citation statements)

References 28 publications

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“…7,11 The incidence of amenorrhea depends on chemotherapeutic agent and dose, and patient's age at time of treatment, younger women being less likely to develop premature ovarian failure. [5][6][7] Severe impairment of gonadal function is relatively rare after conventional chemotherapy for acute leukemia. The spinal component of craniospinal irradiation seems to be the major risk factor, but cyclophosphamide may also be contributory.…”

Section: Discussionmentioning

confidence: 99%

“…1,3,4 Cytotoxics are known to induce ovarian toxicity in adults, dependent upon type of agent, dosage, administration schedule and patient age. [5][6][7] Much less is known about the effects of high-dose chemotherapy on ovarian function in children. 2,8,9 We report an analysis of ovarian function in long-term survivors following myeloablative chemotherapy and bone marrow transplantation.…”

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confidence: 99%

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Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure

Teinturier

Hartmann

Valteau‐Couanet

et al. 1998

Bone Marrow Transplant

194

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Summary:We studied pubertal status and ovarian function in 21 girls aged 11-21 years who had earlier received 1.2-13 years (median 7 years) high-dose chemotherapy and autologous BMT without TBI for malignant tumors. Ten of them were given busulfan (600 mg/m 2 ) and melphalan (140 mg/m 2 ) with or without cyclophosphamide (3.6 g/m 2 ). Eleven others did not receive busulfan. Twelve girls (57%) had clinical and hormonal evidence of ovarian failure. Among nine others who had completed normal puberty, six had normal gonadotropin levels, one had elevated gonadotropin levels and two had gonadotropin levels at the upper limit of normal. The 10 girls who received busulfan all developed severe and persistent ovarian failure. High-dose busulfan is therefore a major cause of ovarian failure even when given in the prepubertal period. These findings emphasize the need for long-term endocrine follow-up of these patients in order to initiate estrogen replacement therapy. Keywords: ovarian function; high-dose chemotherapy; bone marrow transplantation; busulfan; childhood Increasing numbers of children who receive hematopoietic stem cell transplants (HSCT) for malignancies now survive. It is therefore important to evaluate ovarian toxicity secondary to the therapeutic regimens. New chemotherapy protocols will have to aim towards effecting long-term survival with minimal late morbidity. Chemotherapy is used alone or in combination with total body irradiation. Total body irradiation, used in the preparative regimens for hematologic malignancies, is deleterious to gonadal function. 1,2 Myeloablative therapy consisting of cyclophosphamide, busulfan or melphalan, has been used as an alternative to avoid the side-effects of irradiation on endocrine functions and growth. 1,3,4 Cytotoxics are known to induce ovarian toxicity in adults, dependent upon type of agent, dosage, administration schedule and patient age. 5-7 Much less is known about the effects of high-dose chemotherapy on ovarian function in children. 2,8,9 We report an analysis of ovarian function in long-term survivors following myeloablative chemotherapy and bone marrow transplantation. Patients and methodsWe screened all long-term female survivors older than 11 years who had received high-dose chemotherapy and autologous bone marrow transplantation without abdominal or pelvic radiation for malignant tumors at Institut Gustave Roussy. Twenty-one girls fulfilled these criteria.At time of transplantation, they were aged 2-17 years (median 9 years). Pubertal development was evaluated clinically according to Tanner. 10 Fourteen girls were prepubertal (stage 1), two were undergoing puberty (stage 3) and five had regular menses (stage 5). No hormonal evaluation was carried out before chemotherapy, but pubertal stages of all the patients were appropriate for their age.The study took place 1.2-13 years (median 7 years) after bone marrow transplantation and discontinuation of chemotherapy. At time of study, girls were aged 11.5-21 years (median 14.5 years).Serum concentrations of 17...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure

Teinturier

Hartmann

Valteau‐Couanet

et al. 1998

Bone Marrow Transplant

194

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“…Testicular biopsy showed an absence of germinal epithelium. Mean testosterone levels were normal and LH levels were at or just above the upper limit of normal (Chapman et al, 1979). 10 out of 11 patients studied between 6 and 8 years post completion of therapy with MVPP or chlorambucil VPP, were azoospermic (Whitehead et al, 1982).…”

Section: Chemotherapymentioning

confidence: 90%

Gonadal function in men with chronic illness

Turner

Wass

1997

Clinical Endocrinology

104

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“…This is particularly true of gonadal function in patients with HD, which commonly affects young people who may not have started or completed a family when the diagnosis is made. Both MOPP and MVPP were found to produce a very high incidence of azoospermia, with only a few men recovering spermatogenesis after treatment (Chapman et al, 1979;Whitehead et al, 1982). Procarbazine, a component of both regimens, causes complete aplasia of the germinal epithelium in the rat (Jackson et al, 1961) and the non-human primate (Sieber et al, 1978), and mustine and vinblastine are also implicated in the germinal epithelial damage following MOPP/MVPP (Spitz, 1948;Vilar, 1975).…”

Section: Discussionmentioning

confidence: 99%

“…Following conventional MOPP-like combinations, azoospermia is inevitable in males (Chapman et al, 1979;Whitehead et al, 1982). A pilot study to investigate fertility in men treated with VAPEC-B chemotherapy was therefore undertaken.…”

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confidence: 99%

Male fertility after VAPEC-B chemotherapy for Hodgkin's disease and non-Hodgkin's lymphoma

Radford

Clark²,

Crowther³

et al. 1994

Br J Cancer

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Summary Semen analysis was performed in 14 men a median of 13.5 months after completion of VAPEC-B chemotherapy for Hodgkin's disease or non-Hodgkin's lymphoma. Semen from 12 patients contained motile spermatozoa, and in nine cases the count was >20 million ml'. One patient was azoospermic (VAPEC-B followed by pelvic radiotherapy) and another had a count of 21 millionml1' but sperm were non-motile. These findings suggest that, in the majority of cases, VAPEC-B chemotherapy does not cause permanent damage to the male germinal epithelium. A more detailed study of gonadal function in males and females before and after treatment with VAPEC-B for Hodgkin's disease is currently in progress.

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Cyclical Combination Chemotherapy and Gonadal Function

Cited by 238 publications

References 28 publications

Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure

Ovarian function after autologous bone marrow transplantation in childhood: high-dose busulfan is a major cause of ovarian failure

Gonadal function in men with chronic illness

Male fertility after VAPEC-B chemotherapy for Hodgkin's disease and non-Hodgkin's lymphoma

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