Allogeneic Hematopoietic cell Transplantation Using Alemtuzumab in Asian Patients with Inborn Errors of Immunity

• Published in: Journal of clinical immunology 2024-08, Vol.44 (6), p.126, Article 126
• Main Authors: Miyamoto, Satoshi, Niizato, Daiki, Tomomasa, Dan, Nishimura, Akira, Hoshino, Akihiro, Kamiya, Takahiro, Isoda, Takeshi, Takagi, Masatoshi, Kajiwara, Michiko, Azumi, Shohei, Hirabayashi, Shinsuke, Sakamoto, Kenichi, Kishimoto, Kenji, Miyamura, Takako, Umeda, Katsutsugu, Hirose, Ayana, Keino, Dai, Yanagimachi, Masakatsu, Kanda, Kaori, Sakai, Yuta, Ikawa, Yasuhiro, Watanabe, Kenichiro, Tanaka, Keisuke, Mori, Takehiko, Ichinohe, Tatsuo, Sakaguchi, Hirotoshi, Morio, Tomohiro, Kanegane, Hirokazu
• Format: Article
• Language: English
• Subjects: Adolescent; Alemtuzumab - therapeutic use; Allografts; Asian People; Biomedical and Life Sciences; Biomedicine; Blood cells; Busulfan; CD4 antigen; Child; Child, Preschool; Chimerism; East Asian People; Female; Fludarabine; Graft vs Host Disease - etiology; Graft-versus-host reaction; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Humans; Immune System Diseases - genetics; Immunity; Immunology; Infant; Infectious Diseases; Internal Medicine; Japan; Lymphocytes T; Male; Medical Microbiology; Monoclonal antibodies; Retrospective Studies; Stem cell transplantation; T cell receptors; Toxicity; Transplantation Conditioning - methods; Transplantation, Homologous; Treatment Outcome; Viral infections
• ISSN: 0271-9142; 1573-2592; 1573-2592
• DOI: 10.1007/s10875-024-01734-5

Alemtuzumab is used with reduced-toxicity conditioning (RTC) in allogeneic hematopoietic cell transplantation (HCT), demonstrating efficacy and feasibility for patients with inborn errors of immunity (IEI) in Western countries; however, the clinical experience in Asian patients with IEI is limited. We retrospectively analyzed patients with IEI who underwent the first allogeneic HCT with alemtuzumab combined with RTC regimens in Japan. A total of 19 patients were included and followed up for a median of 18 months. The donors were haploidentical parents ( n  = 10), matched siblings ( n  = 2), and unrelated bone marrow donors ( n  = 7). Most patients received RTC regimens containing fludarabine and busulfan and were treated with 0.8 mg/kg alemtuzumab with intermediate timing. Eighteen patients survived and achieved stable engraftment, and no grade 3–4 acute graft-versus-host disease was observed. Viral infections were observed in 11 patients (58%) and 6 of them presented symptomatic. The median CD4 + T cell count was low at 6 months (241/µL) but improved at 1 year (577/µL) after HCT. Whole blood cells continued to exhibit > 80% donor type in most cases; however, 3/10 patients exhibited poor donor chimerism only among T cells and also showed undetectable levels of T-cell receptor recombination excision circles (TRECs) at 1 year post-HCT. This study demonstrated the efficacy and safety of alemtuzumab; however, patients frequently developed viral infections and slow reconstitution or low donor chimerism in T cells, emphasizing the importance of monitoring viral status and T-cell-specific chimerism. (238