Allogeneic Hematopoietic Stem Cell Transplantation for Aplastic Anemia with Pre-Transplant Conditioning Using Fludarabine, Reduced-Dose Cyclophosphamide, and Low-Dose Thymoglobulin:Â Ksgct Prospective Study

• Published in: Blood 2018-11, Vol.132 (Supplement 1), p.2101-2101
• Main Authors: Kako, Shinichi, Kanda, Yoshinobu, Onizuka, Makoto, Aotsuka, Nobuyuki, Usuki, Kensuke, Tachibana, Takayoshi, Kobayashi, Takeshi, Kato, Jun, Yano, Shingo, Shimizu, Hiroaki, Shono, Katsuhiro, Tanaka, Masatsugu, Tsukamoto, Shokichi, Mori, Takehiko, Yamazaki, Etsuko, Okamoto, Shinichiro
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2018-99-115105

▪ [Background] Allogeneic hematopoietic stem cell transplantation (HSCT) is a potent treatment to cure in patients with aplastic anemia (AA). However, an optimal pre-transplant conditioning remains unclear. The combination of high-dose cyclophosphamide (CY) and anti-thymocyte globulin (ATG) has been used as an effective conditioning, but cardiotoxity due to high-dose CY has been a major concern especially in patients with iron overload by excessive transfusion. In addition, the appropriate dose and timing of ATG use is another unsolved topic in HSCT for AA. Therefore, we performed a prospective study to assess the safety and efficacy of a conditioning regimen using fludarabine (Flu), reduced-dose CY, and low-dose thymoglobulin in HSCT for AA. [Methods] Patients with severe AA, aged between 16 and 65 years, who have an HLA-matched or 1-locus mismatched, related or unrelated donor were prospectively included. A conditioning regimen consisted of Flu 30mg/m2 for 4 days, CY 25mg/kg for 4 days, and thymoglobulin 1.25mg/kg for 2 days (days -4, and -3). In patients who underwent transplantation from unrelated and/or HLA-mismatched donor, 2 Gy of total body irradiation was added. Cyclosporine for an HLA-matched related donor or tacrolimus for the other donors, together with short-term methotrexate were used as graft-versus-host disease (GVHD) prophylaxis. Granulocyte-colony stimulating factor was used from 1 day after transplantation. Primary outcome measure was an overall survival at 1 year after HSCT. This study was approved by the Institutional Review Board of all the participating institutions. [Results] Twenty-eight patients were enrolled between 2011 and 2017, and their median age was 36 years (range: 18 - 61y). Sixteen patients were male. A median time from diagnosis to transplantation was 1858 days in patients who had previously received immunosuppressive therapy (IST) using ATG (n = 16) and 121 days in those who had not received IST (n = 12). Sixteen patients received graft form related donors including 1 HLA-mismatched donor, and 12 patients did from unrelated donors including 3 mismatched donors. Stem cell source was bone marrow in 27 out of 28 patients. All patients but one, who died early due to infection, achieved neutrophil engraftment at a median of 19 days after HSCT. Mixed chimerism (MC) was observed in 6 patients at day 30, and 3 out of those 6 patients achieved complete donor chimerism by day 90. On the other hand, MC was newly observed in addit