title: In vivo T-cell depletion with alemtuzumab in allogeneic hematopoietic stem cell transplantation: Combined results of two studies on aplastic anemia and HLA-mismatched haploidentical transplantation.
abstract: We evaluated the efficacy of in vivo T-cell depletion with alemtuzumab in two prospective studies according to the International Conference on Harmonisation (ICH)-Good Clinical Practice (ICH-GCP) guidelines; one was for patients with aplastic anemia (AA study) and the other was for patients who were undergoing hematopoietic stem cell transplantation (HSCT) from a 2- or 3-antigen-mismatched haploidentical donor (MM study). The final dose of alemtuzumab in these studies was 0.16 mg/kg/day for 6 days. At this dose, all of the 12 and 11 patients in the AA and MM studies, respectively, achieved initial engraftment and the incidences of Grade II-IV acute graft-versus-host disease (GVHD) were 0% and 18%. While cytomegalovirus (CMV) frequently reactivated, none of the patients developed fatal CMV disease. Transplantation-related mortality within 1 year after HSCT was observed in only two and one patients, respectively. The numbers of CD4+ and CD8+ T-cells and T-cell receptor rearrangement excision circles remained low within 1 year after HSCT. These findings suggest that the use of alemtuzumab at this dose in a conditioning regimen enables safe allogeneic HSCT even from a 2- or 3-antigen-mismatched donor. However, the use of a lower dose of alemtuzumab should be explored in future studies to accelerate immune recovery after HSCT.
authors: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan. ycanda-tky@umin.ac.jp
authors: Yoshinobu
authors: Y
authors: Kanda
authors: Kumi
authors: K
authors: Oshima
authors: Shinichi
authors: S
authors: Kako
authors: Takahiro
authors: T
authors: Fukuda
authors: Naoyuki
authors: N
authors: Uchida
authors: Koichi
authors: K
authors: Miyamura
authors: Yukio
authors: Y
authors: Kondo
authors: Shinji
authors: S
authors: Nakao
authors: Koji
authors: K
authors: Nagafuji
authors: Toshihiro
authors: T
authors: Miyamoto
authors: Mineo
authors: M
authors: Kurokawa
authors: Yasushi
authors: Y
authors: Okoshi
authors: Shigeru
authors: S
authors: Chiba
authors: Yasuo
authors: Y
authors: Ohashi
authors: Yoichi
authors: Y
authors: Takaue
authors: Shuichi
authors: S
authors: Taniguchi
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D000741:Anemia, Aplastic / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D003520:Cyclophosphamide / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology; D006680:HLA Antigens / Q000276:immunology; D006239:Haplotypes; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D006801:Humans; D018655:Lymphocyte Count; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D014740:Vidarabine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D006680:HLA Antigens; D000074323:Alemtuzumab; D003520:Cyclophosphamide; D014740:Vidarabine; C024352:fludarabine