Impact of the presence of HLA 1-locus mismatch and the use of low-dose antithymocyte globulin in unrelated bone marrow transplantation

• Published in: Bone marrow transplantation (Basingstoke) Vol. 52; no. 10; pp. 1390 - 1398
• Main Authors: Kawamura, K, Kanda, J, Fuji, S, Murata, M, Ikegame, K, Yoshioka, K, Fukuda, T, Ozawa, Y, Uchida, N, Iwato, K, Sakura, T, Hidaka, M, Hashimoto, H, Ichinohe, T, Atsuta, Y, Kanda, Y
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-10-2017; Nature Publishing Group
• Subjects: 631/250/1904; 692/699/1541/1990/283; Acute Disease; Adolescent; Adult; Aged; Analysis; Antilymphocyte serum; Antilymphocyte Serum - administration & dosage; Antilymphocyte Serum - adverse effects; Bone marrow; Bone Marrow Transplantation; Cell Biology; Comparative analysis; Disease-Free Survival; Donor Selection; Female; Globulins; Graft vs Host Disease - mortality; Graft vs Host Disease - prevention & control; Graft-versus-host reaction; Health aspects; Hematologic Neoplasms - mortality; Hematologic Neoplasms - therapy; Hematology; Hematopoietic stem cells; Histocompatibility antigen HLA; Histocompatibility Testing; HLA Antigens; Human leukocyte antigen test; Humans; Internal Medicine; Leukemia; Loci; Male; Medicine; Medicine & Public Health; Middle Aged; Mortality; Mud; Myelodysplastic syndrome; Myelodysplastic syndromes; original-article; Patients; Public Health; Stem cell transplantation; Stem Cells; Survival Rate; Thymocytes; Thymoglobulin; Transplantation; Unrelated Donors
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/bmt.2017.153

HLA 1-locus-mismatched unrelated donors (1MMUD) have been used in allogeneic hematopoietic stem cell transplantation (allo-HCT) for patients who lack an HLA-matched donor. We retrospectively analyzed 3313 patients with acute leukemia or myelodysplastic syndrome who underwent bone marrow transplantation from an HLA allele-matched unrelated donor (MUD) or 1MMUD between 2009 and 2014. We compared the outcomes of MUD (
n
=2089) and 1MMUD with antithymocyte globulin (ATG) (1MM-ATG(+);
n
=109) with those of 1MMUD without ATG (1MM-ATG(−);
n
=1115). The median total dose of ATG (thymoglobulin) was 2.5 mg/kg (range 1.0–11.0 mg/kg) in the 1MM-ATG(+) group. The rates of grade III–IV acute GvHD, non-relapse mortality (NRM) and overall mortality were significantly lower in the MUD group than in the 1MM-ATG(−) group (hazard ratio (HR) 0.77,
P
=0.016; HR 0.74;
P
<0.001; and HR 0.87,
P
=0.020, respectively). Likewise, the rates of grade III–IV acute GVHD, NRM and overall mortality were significantly lower in the 1MM-ATG(+) group than in the 1MM-ATG(−) group (HR 0.42,
P
=0.035; HR 0.35,
P
<0.001; and HR 0.71,
P
=0.042, respectively). The outcome of allo-HCT from 1MM-ATG(−) was inferior to that of allo-HCT from MUD even in the recent cohort. However, the negative impact of 1MMUD disappeared with the use of low-dose ATG without increasing the risk of relapse.