|
|||||
|
|
Hematopoietic Cell Transplantation with Reduced Intensity Conditioning Using Fludarabine/Busulfan or Fludarabine/Melphalan for Primary Immunodeficiency Diseases |
|
| Authors: | Nishimura Akira Aoki Yuki Ishiwata Yasuyoshi Ichimura Takuya Ueyama Junichi Kawahara Yuta Tomoda Takahiro Inoue Maiko Matsumoto Kazuaki Inoue Kento Hiroki Haruka Ono Shintaro Yamashita Motoi Okano Tsubasa Tanaka-Kubota Mari Ashiarai Miho Miyamoto Satoshi Miyawaki Reiji Yamagishi Chika Tezuka Mari Okawa Teppei Hoshino Akihiro Endo Akifumi Yasuhara Masato Kamiya Takahiro Mitsuiki Noriko Ono Toshiaki Isoda Takeshi Yanagimachi Masakatsu Tomizawa Daisuke Nagasawa Masayuki Mizutani Shuki Kajiwara Michiko Takagi Masatoshi Kanegane Hirokazu Imai Kohsuke Morio Tomohiro |
| Affiliation: | 1.Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan ;2.Department of Hospital Pharmacy, Tokyo Medical and Dental University (TMDU), Tokyo, Japan ;3.Department of Pediatrics, Yamaguchi University Hospital, Yamaguchi, Japan ;4.Department of Pediatrics, Tottori University Hospital, Tottori, Japan ;5.Department of Pediatrics, Jichi Medical University School of Medicine, Shimotsuke, Japan ;6.Department of Pharmacokinetics and Pharmacodynamics, Tokyo Medical and Dental University (TMDU), Tokyo, Japan ;7.Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan ;8.Department of Transfusion Medicine and Cell Therapy, Tokyo Medical and Dental University (TMDU), Medical Hospital, Tokyo, Japan ;9.Department of Child Health and Development, Tokyo Medical and Dental University (TMDU), Tokyo, Japan ;10.Department of Community Pediatrics, Perinatal, and Maternal Medicine, Tokyo Medical and Dental University (TMDU), 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan ; |
| Abstract: | Purpose The purpose of our study was to compare the safety and efficacy of hematopoietic cell transplantation (HCT) using fludarabine (Flu)-based reduced intensity conditioning (RIC) with busulfan (BU) or melphalan (Mel) for primary immunodeficiency diseases (PID). MethodsWe retrospectively analyzed transplant outcome, including engraftment, chimerism, immune reconstitution, and complications in 15 patients with severe combined immunodeficiency (SCID) and 27 patients with non-SCID PID. The patients underwent Flu-based RIC-HCT with BU (FluBU: 7 SCID, 16 non-SCID) or Mel (FluMel: 8 SCID, 11 non-SCID). The targeted low-dose BU with therapeutic drug monitoring was set to 30 mg hour/L for SCID. ResultsThe 2-year overall survival of all patients was 79.6% and that of patients with SCID in the FluBU and FluMel groups was 100% and 62.5%, respectively. In the FluBU group, all seven patients achieved engraftment, good immune reconstitution, and long-term survival. All five patients receiving umbilical cord blood transplantation achieved complete or high-level mixed chimerism and sufficient specific IgG production. In the FluMel group, six of eight patients achieved complete or high-level mixed chimerism. Viral reactivation or new viral infection occurred in one FluBU group patient and four FluMel group patients. In the non-SCID group, 10 of 11 patients (91%) who received FluMel achieved complete or high-level mixed chimerism but had variable outcomes. Patients with WAS (2/2 patients), NEMO deficiency (2/2 patients), and X-linked hyper IgM syndrome (2/3 patients) who received FluBU achieved complete or high-level mixed chimerism and long-term survival. ConclusionsRIC-HCT with FluBU is a safe and effective strategy for obtaining high-level donor chimerism, immune reconstitution including B cell function, and long-term survival in patients with SCID. In patients with non-SCID PID, the results varied according to the subtype of the disease. Further prospective studies are required to optimize the conditioning regimen for non-SCID PID. |
| Keywords: | |
| 本文献已被 SpringerLink 等数据库收录！ | |