title: Reduced-intensity allogeneic transplantation using alemtuzumab from HLA-matched related, unrelated, or haploidentical related donors for patients with hematologic malignancies.
abstract: We present a comparative study on 124 patients with hematologic malignancies who had undergone reduced-intensity conditioning and then received a transplant from an HLA-matched related (MRD), an HLA-matched unrelated (MUD), or an HLA-haploidentical related (HAPLO) donor. The conditioning regimen, which consisted of fludarabine, melphalan or busulfan, and alemtuzumab was administered to patients with lymphoid (n = 62) or myeloid disease (n = 62). Mycophenolate mofetil was used as prophylaxis for graft-versus-host disease (GVHD), and 38, 58, and 33 patients received transplants from MRD, MUD, and HAPLO donors, respectively. Only 2 patients experienced primary graft failure (GF) after melphalan-based regimen, whereas 8 of the 17 patients who received a transplant from HAPLO donors experienced a primary GF after busulfan-based regimen. The cumulative incidence of grade III to IV acute GVHD in engrafted patients who had received transplants from MRD, MUD, or HAPLO donors was 3%, 11%, and 27%, respectively, and the 2-year overall survival (OS) rates were 51%, 22%, and 23%, respectively. According to multivariate analysis, transplantation from either MUD or HAPLO donors compared with MRD were adverse factors that affected the OS (P = .006 and P = .002, respectively). In conclusion, the reduced-intensity regimen that included fludarabine, busulfan, or melphalan and alemtuzumab using only mycophenolate mofetil as the GVHD prophylaxis conferred favorable outcomes in the MRD group but lower survival rates in the MUD and HAPLO groups. The busulfan-based regimen led to a high incidence of GF in the HAPLO group, suggesting the need for modification or intensification of immunosuppression.
authors.affiliation: Adult Stem Cell Transplant Program, Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina; Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan. Electronic address: jkandajp@gmail.com.
authors.forename: Junya
authors.initials: J
authors.lastname: Kanda
authors.affiliation: Adult Stem Cell Transplant Program, Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Gwynn D
authors.initials: GD
authors.lastname: Long
authors.affiliation: Adult Stem Cell Transplant Program, Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gasparetto
authors.affiliation: Adult Stem Cell Transplant Program, Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Horwitz
authors.affiliation: Adult Stem Cell Transplant Program, Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Sullivan
authors.affiliation: Adult Stem Cell Transplant Program, Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: John P
authors.initials: JP
authors.lastname: Chute
authors.affiliation: Adult Stem Cell Transplant Program, Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Ashley
authors.initials: A
authors.lastname: Morris
authors.affiliation: Adult Stem Cell Transplant Program, Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Michael
authors.initials: M
authors.lastname: Shafique
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Adult Stem Cell Transplant Program, Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: Nelson J
authors.initials: NJ
authors.lastname: Chao
authors.affiliation: Adult Stem Cell Transplant Program, Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors.forename: David A
authors.initials: DA
authors.lastname: Rizzieri
mesh_terms: D000328:Adult; D000368:Aged; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006680:HLA Antigens; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014019:Tissue Donors; D019172:Transplantation Conditioning / Q000009:adverse effects*; D014184:Transplantation, Homologous / Q000009:adverse effects*; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D006680:HLA Antigens; D000074323:Alemtuzumab
keywords: Alemtuzumab; Haploidentical; Matched-related; Matched-unrelated; Reduced-intensity