Reproductive status in long-term bone marrow transplant survivors receiving busulfan-cyclophosphamide (120 mg/kg)

Abstract

Summary:There are few published data on the recovery of fertility after 'little' Bu-Cy (busulfan 16 mg/kg, cyclophosphamide 120 mg/kg) conditioning for BMT. To address this, we identified 19 females aged less than 40 years at transplant and 47 males from a single centre who were alive a minimum of 2 years after BMT with little Bu-Cy as conditioning and who were evaluable for testing. FSH, LH, testosterone and inhibin B levels were measured in males. Twenty-six also had semen analysis, a median of 5 years post transplant; 21 had detectable sperm, with 11 having counts Ͼ20 × 10 6 /ml. There was an association between prolonged chronic graft-versus-host disease and low sperm counts. FSH and inhibin B levels correlated with sperm counts but not to the extent that they could reliably predict counts in individual patients. An additional six of seven males attempting to father children did so, a median of 3.2 years post transplant. Low testosterone levels were noted in 12% of males, most of whom had symptoms consistent with androgen deficiency. FSH, LH and oestradiol levels in the absence of hormone replacement therapy were measured in females; all remained amenorrheic with endocrine evidence of ovarian failure. These results have implications for fertility counselling and hormone replacement therapy both pre-and post BMT. Bone Marrow Transplantation (2000) 26, 1089-1095. Keywords: busulfan; cyclophosphamide; marrow transplantation; fertility; testosterone Myeloablative conditioning regimens comprising high dose combination alkylating agents have been conventionally considered to cause permanent infertility in the vast majority of adult patients of either sex undergoing allogeneic or autologous marrow or peripheral blood stem cell transplantation. The most widely used non-total body irradiation (TBI) regimen prior to allografting is busulfancyclophosphamide (Bu-Cy). To our knowledge, the only substantial peer-reviewed publication of the effects of BuCy on fertility has been published by the Seattle group in

Semen analysis following allogeneic bone marrow transplantation. Additional data for evidence-based counselling

“…A recent publication evaluating the effect of the busulfan-cyclophosphamide conditioning regimen for BMT reported detectable sperm in 21 of the 26 men studied, a median of 5 years post transplant. 16 The present study, reporting results of 99 semen samples obtained following BMT in 64 patients, provides additional information supporting patient counselling and the need for planning more precise timing of follow-up semen analysis in these patients.…”

Germ cell damage and Leydig cell insufficiency in recipients of nonmyeloablative transplantation for haematological malignancies

“…3 Although it may be expected that multiagent chemotherapy such as BEAM will induce more gonadal injury than melphalan and fludarabine alone, we have shown evidence of testicular injury even with fludarabine used as monotherapy in a patient with CLL. 9 Although there are no human data on reproductive or gonadotoxic potential in our nonmyeloablative protocol, melphalan protocols are less gonadotoxic than others using busulphan/cyclophosphamide or cyclophosphamide alone 11 based on an increased number of pregnancies. 12 However, these studies did not look into sperm parameters or gametogenic/steroidogenic endocrine function.…”

Fertility Preservation in Young Women Undergoing Breast Cancer Therapy

“…Nevertheless, because younger patients have a larger ovarian reserve, they might tolerate some loss in the follicular pool, and immediate ovarian function might not be affected in the short term. All patients who receive high-dose gonadotoxic chemotherapy will eventually suffer from premature ovarian failure [70,71]. In the absence of a prospective randomized study with sufficient power, we do not rely on ovarian suppression as an effective means of fertility preservation.…”