Preserving Fertility in Females Receiving Autologous Bone Marrow Transplants
Preserving Fertility in Females Receiving Autologous Bone Marrow Transplants
ABSTRACT & COMMENTARY
Synopsis: In this report, a marrow preparative regimen used at two hospitals in the United Kingdom (Royal Victoria Infirmary, Newcastle-on-Tyne, and Ninewells Hospital, Dundee) was found to be associated both with excellent long-term survival and maintained fertility.
Source: Jackson GH, et al. Leuk Lymphoma 1997;28: 127-132.
With increased use of peripheral blood stem cell or autologous bone marrow transplantation for a variety of malignancies, various preparative regimens have been developed. In selecting the appropriate regimen for young patients, particularly those who are being treated with curative intention, the issue of the effects of such therapy on fertility should be considered. In males, there has been reasonable success with sperm banking before treatment. Analogous procedures in women (oocyte or embryo preservation) are still considered experimental and are not generally available. In this report from two hospitals in the United Kingdom, the experience with a specific preparative regimen was examined with attention to both long-term survival and maintenance of fertility in women younger than 40 years. Patients in first or second remission with high-risk Hodgkin’s disease (HD) or non-Hodgkin’s lymphoma (NHL) were treated with marrow ablation and autologous marrow rescue. Remission was induced in the HD patients with an eight-drug regimen, PVACE-BOP (prednisolone, vinblastine, doxorubicin, chlorambucil, etoposide, bleomycin, vincristine, and procarbazine). NHL patients received six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone). The marrow-conditioning regimen for the HD disease patients was etoposide 1.6 gm/m2 by 20-hour infusion and melphalan 3 mg/kg as a single dose. The NHL patients received either the same regimen as the HD patients, or just the melphalan alone. Of the 71 patients so treated at these hospitals, 23 were females younger than 40 years. Of these, 10 patients were able to conceive and have successful pregnancies and normal deliveries. In the group, there were three multiple pregnancies, including two twin pregnancies and one triplet pregnancy. The time from transplantation to conception varied from 8-69 months. Of particular note, all of the women who received autologous marrow transplantation with these regimens who expressed a desire to become pregnant were successful, and none of the pregnancies were artificially assisted. Also of note, the five-year event-free survival for the group of 73 patients receiving this marrow conditioning approach for these disorders ranged from 60-91% depending on the disease, age group, and whether the transplant was during the first or second remission. The results compare favorably with published series using other marrow preparative regimens.COMMENTARY
One could find fault with this report because it is not a large series nor was it a randomized trial. However, it is difficult to refute the outstanding level of success in treatment outcome and fertility using this preparative regimen. Of course, it is not clear what the fertility success rate is using other approaches, but it is probable that most are not this successful. Jackson and colleagues offer a suggestive point. One of the two participating hospitals, Royal Victoria Infirmary, Newcastle-on-Tyne (at which 61 of the 73 transplants were performed) registers its patients with the European Bone Marrow Transplantation Registry. In the registry, only 17 unassisted pregnancies in transplant recipients have been reported, and eight of these were from this single institution.Most of the published experience regarding fertility after bone marrow transplantation is with allogeneic bone marrow recipients. In the large centers, such as that at the University of Washington in Seattle, subsequent pregnancies are uncommon, especially when total body irradiation is part of the conditioning regimen.1 However, this same group reported 58 pregnancies in 28 patients who had been allografted with single-agent cyclophosphamide as the conditioning approach.2 Thus, it appears that in addition to the type of marrow reconstitution (allograft vs autograft), preparative regimen itself influences subsequent fertility with the less aggressive, single-agent approach offering advantages.
Of course, the desire to preserve fertility needs to be considered a priority secondary to obtaining long-term survival. Yet, the experience with both allogeneic and autologous transplants indicate that certain preparative approaches, such as the single-agent melphalan conditioning reported in this paper, under appropriate circumstances results in excellent results in both survival and fertility. The results in this paper are surprising both from the point of view of efficacy and from the point of view of fertility. The patients had all received alkylating agent-containing conventional-dose chemotherapy regimens, and procarbazine was a component of the Hodgkin’s disease regimen. It is known that female fertility is maintained in the vast majority of MOPP-treated (nitrogen mustard, vincristine, procarbazine, and prednisone) women younger than 26 years at the time of treatment.3 Yet, fertility is lost in nearly 90% of those treated at age 26 or older. Jackson et al examined women under age 40; however, it seems quite likely that all the women who successfully became pregnant were in their 20s, based on prior work. The paper, even with its limitations, provides a useful description of an excellent clinical experience of bone marrow transplantation in young women who maintain the hope of future pregnancy. However, until further data are produced substantiating the high survival and fertility rate with high-dose melphalan, one should be cautious about advising one’s female patients in their 30s that post-treatment fertility is a reasonable expectation.
References
1. Sanders JE, et al. J Clin Oncol 1988;6:813-818.2. Sanders JE, et al. Blood 1996;87:3045-3052.
3. Schilsky RL, et al. Am J Med 1981;71:552.
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