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CORRESPONDENCE Increasing numbers of young women are being cured by
chemotherapy for aggressive non-Hodgkin lymphoma (NHL), and the
possibility of fertility preservation after these treatments has
received much attention. The most important risk factors for the
development of ovarian failure are the woman's age at the time of
first treatment and the number of cycles with alkylating
agents.1 High-dose chemotherapy with autologous stem cell
transplantation (ASCT) is now an accepted curative therapy for young
patients with high-risk NHL.2 Very few reported
pregnancies have been published after such intensive regimens, mainly
because they were performed after relapse in heavily pretreated
women.3 To determine the role of the cumulative
cyclophosphamide dose given sequentially or in a single dose with ASCT,
we decided to analyze the pregnancy rate for all young women
prospectively treated according to the lymphome non-Hodgkinieu (LNH)
87-2 protocol for aggressive NHL. This protocol included 1043 patients at 35 participating centers. Inclusion criteria and clinical
results have been published.4 Briefly, patients with newly
diagnosed NHL were given chemotherapy ACVB (doxorubicin,
cyclophosphamide, vinblastine, and bleomycin), 4 cycles and responding
patients were randomized to receive sequential chemotherapeutic (CT)
consolidation or a consolidative CBV regimen (cyclophosphamide 6 g/m2, BCNU [carmustine] 300 mg/m2
and VP16 [etoposide] 1000 mg/m2) followed by ASCT. The
total dose of cyclophosphamide (the main toxic drug for ovarian
failure) was 10 800 mg/m2 at the end of the procedure for
the patients undergoing high-dose therapy and 7800 mg/m2
for those given the sequential CT. Radiation therapy was not included
in the protocol. Only women under 41 years of age at diagnosis were
considered for the pregnancy rate evaluation. Among the 210 young women
(median age at diagnosis: 27 years; range, 15-40 years), 109 were
randomized for the consolidation: 56 had received the intensive arm and
53 the sequential chemotherapy. No hormonal treatment was mandatory,
and no specific recommendation was given for further pregnancy.
Fourteen women included in this prospective protocol had conceived at
the last follow-up evaluation (December 1999). They had all received
the planned treatment (intensive or sequential), and only 1 patient
relapsed, received further treatment, and died; the remaining 13 women
are alive in complete remission. See Table
1 for details.
We found that a small number of normal pregnancies can be achieved in women treated with chemotherapy for NHL whether or not high-dose therapy with ASCT is included. The pregnancy rate did not seem to have been impaired in the group treated with high-dose chemotherapy despite a total cyclophosphamide dose of 10 800 mg/m2. On the other hand, these pregnancies occurred in the youngest patients and no pregnancy was observed in women over 29 years at NHL diagnosis in this group. The influence of age on ovarian function recovery after ASCT has already been published,5 and some rare pregnancies have been published in recipients of allogeneic transplantation including total body irradiation (TBI).6 In conclusion, the youngest patients at diagnosis of NHL can hope to recover normal fertility after first-line therapy even when high-dose chemotherapy is given; no birth defects have been observed, but a follow-up of the children is warranted. For the remaining women who wish to become pregnant after treatment, alternative chemotherapeutic regimens with lower doses of alkylating agents or other agents should be prescribed until oocyte or ovarian cryopreservation become routinely available.7
Pauline Brice, Corinne Haioun, Marc André, and Christian Gisselbrecht, for the Groupe
d'Etude des Lymphomes de l'Adulte
References 1. Apperley JF, Reddy N. Mechanism and management of treatment-related gonadal failure in recipients of high-dose chemoradiotherapy. Blood Rev. 1995;9:93-116[CrossRef][Medline] [Order article via Infotrieve].
2.
Gianni AM, Bregni M, Siena S, et al.
High-dose chemotherapy and autologous bone marrow transplantation compared with MACOP-B in aggressive B-cell lymphoma.
N Engl J Med.
1997;336:1290-1297 3. Gulati SC, Van Poznak C. Pregnancy after bone marrow transplantation. J Clin Oncol. 1998;16:1978-1985[Abstract].
4.
Haioun C, Lepage E, Gisselbrecht C, et al.
Survival benefit of high-dose therapy in poor-risk aggressive non-Hodgkin's lymphomas: final analysis of the prospective LNH 87-2 protocol.
J Clin Oncol.
2000;18:3025-3030 5. Schimmer AD, Quatermain M, Imrie K, et al. Ovarian function after autologous bone marrow transplantation. J Clin Oncol. 1998;16:2359-2363[Abstract].
6.
Sanders JE, Hawley J, Levy W, et al.
Pregnancies following high-dose cyclophosphamide with or without high-dose busulfan or TBI and bone marrow transplantation.
Blood.
1996;87:3045-3052 7. Donnez J, Godin PA, Qu J, Nisolle M. Gonadal cryopreservation in the young patients with gynaecologic malignancies. Curr Opin Obstet Gynecol. 2000;12:1-9[CrossRef][Medline] [Order article via Infotrieve].   CiteULike  Connotea  Del.icio.us  Digg  Facebook  Reddit  Technorati  Twitter What's this?
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