Prognostic factors affecting outcome after allogeneic transplantation for hematological malignancies from unrelated donors: results from a randomized trial.
Several prognostic factors for the outcome after allogeneic hematopoietic stem-cell transplant (HSCT) from matched unrelated donors have been postulated from registry data; however, data from randomized trials are lacking. We present analyses on the effects of patient-related, donor-related, and treatment-related prognostic factors on acute GVHD (aGVHD), chronic GVHD (cGVHD), relapse, nonrelapse mortality (NRM), disease-free survival (DFS), and overall survival (OS) in a randomized, multicenter, open-label, phase III trial comparing standard graft-versus-host-disease (GVHD) prophylaxis with and without pretransplantation ATG-Fresenius (ATG-F) in 201 adult patients receiving myeloablative conditioning before HSCT from HLA-A, HLA-B antigen, HLA-DRB1, HLA-DQB1 allele matched unrelated donors. High-resolution testing (allele) of HLA-A, HLA-B, and HLA-C were obtained after study closure, and the impact of an HLA 10/10 4-digit mismatch on outcome and on the treatment effect of ATG-F versus control investigated. Advanced disease was a negative factor for relapse, DFS, and OS. Donor age ≥40 adversely affected the risk of aGVHD III-IV, extensive cGVHD, and OS. Younger donors are to be preferred in unrelated donor transplantation. Advanced disease patients need special precautions to improve outcome. The degree of mismatch had no major influence on the positive effect of ATG-F on the reduction of aGVHD and cGVHD.
Department of Hematology and Oncology, Universitätsklinikum Freiburg, Freiburg, Germany. juergen.finke@uniklinik-freiburg.de
Jürgen
J
Finke
Claudia
C
Schmoor
Wolfgang A
WA
Bethge
Hellmut D
HD
Ottinger
Matthias
M
Stelljes
Axel R
AR
Zander
Liisa
L
Volin
Dominik A
DA
Heim
Rainer
R
Schwerdtfeger
Karin
K
Kolbe
Jiri
J
Mayer
Johan A
JA
Maertens
Werner
W
Linkesch
Ernst
E
Holler
Vladimir
V
Koza
Martin
M
Bornhäuser
Hermann
H
Einsele
Hartmut
H
Bertz
Olga
O
Grishina
Gérard
G
Socié
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D006680:HLA Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use*; D011446:Prospective Studies; D012720:Severity of Illness Index; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D061349:Unrelated Donors
D000961:Antilymphocyte Serum; D006680:HLA Antigens; D019653:Myeloablative Agonists