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Allogeneic stem cell transplantation remains the only curative treatment for sickle cell anemia (SCA), but the place of myeloablative conditioning in the procedure remains to be defined. The aim of the present study was to analyze long-term outcomes, including chimerism, SCA-related events and biological data (hemoglobin, reticulocytes, HbS%), and fertility in a French series of 234 SCA patients under 30 years of age who, from 1988 to 2012, received a matched-sibling-donor stem cell transplantation following standardized myeloablative conditioning [busulfan, cyclophosphamide and rabbit antithymocyte globulin (ATG)]. Since the first report of the series (1988-2004), 151 new consecutive patients with SCA have been similarly transplanted. Considering death, non-engraftment or rejection (donor cells <5%) as events, the 5-year event-free survival was 97.9% (95% confidence interval: 95.5-100%), confirming, since the year 2000, an at least 95% chance of cure. In the overall cohort (n=234, median follow up 7.9 years), event-free survival was not associated with age, but chronic-graft- versus -host disease (cGvHD) was independently associated with recipient's age >15 years (hazard ratio=4.37; P =0.002) and lower (5-15 vs 20 mg/kg) ATG dose (hazard ratio=4.55; P =0.001). At one year, 44% of patients had mixed chimerism (5-95% donor cells), but those prepared with ATG had no graft rejection. No events related to SCA occurred in patients with mixed chimerism, even those with 15-20% donor cells, but hemolytic anemia stigmata were observed with donor cells <50%. Myeloablative transplantation with matched-sibling donor currently has a higher event-free survival (98%) in patients under 30 years of age than that reported for non-myeloablative conditioning (88%). Nevertheless, the risk of cGvHD in older patients and the need to preserve fertility might be indications for a non-myeloablative conditioning., (Copyright© 2020 Ferrata Storti Foundation.)

The risk of developing premature ovarian failure and azoospermia is a major concern in long-term survivors treated for Hodgkin's lymphoma. Alkylating chemotherapy containing procarbazine and/or cyclophosphamide causes prolonged azoospermia in 90-100% of men and premature ovarian failure in 5-25% of women under the age of 30. The risk of infertility increases with the cumulative dose of alkylating agents and the risk is high after salvage therapy including conditioning and autologous or allogeneic transplantation. The doxorubicin-bleomycin-vinblastine-dacarbazine regimen is associated with a lower risk of gonadal damage; the rate of infertility is less than 10%. The risk of premature ovarian failure is limited after the doxorubicin-bleomycin-vinblastine-dacarbazine regimen. However, age is an important factor; women over 30 years of age are at a much higher risk of ovarian failure. Semen cryopreservation should be routinely offered, especially before initial treatment with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone or salvage therapy with high-dose chemotherapy and autologous transplantation. For women with a stable partner, in vitro fertilization for embryo cryopreservation is a routine procedure but can only be offered to a small number of patients and requires a delay in treatment initiation for at least four weeks. Cryopreservation of mature or immature oocytes remains experimental. Ovarian tissue cryopreservation is promising but has so far resulted in only a small number of pregnancies and births. This method, usually involving the removal of an entire ovary, is only proposed before treatment leading to a high risk of infertility. Analogs of LHRH were investigated in order to preserve fertility in women but are not recommended in the absence of studies demonstrating their effectiveness. The risk of secondary infertility should be discussed with patients from the time of the diagnosis and requires multidisciplinary collaboration between hematologists and Assisted Reproductive Techniques (ART) teams.