High day 28 ST2 levels predict for acute graft-versus-host disease and transplant-related mortality after cord blood transplantation.
While cord blood transplantation (CBT) is an effective therapy for hematologic malignancies, acute graft-versus-host disease (aGVHD) is a leading cause of transplant-related mortality (TRM). We investigated if biomarkers could predict aGVHD and TRM after day 28 in CBT recipients. Day 28 samples from 113 CBT patients were analyzed. Suppressor of tumorigenicity 2 (ST2) was the only biomarker associated with grades II-IV and III-IV aGVHD and TRM. Day 180 grade III-IV aGVHD in patients with high ST2 levels was 30% (95% confidence interval [CI], 18-43) vs 13% (95% CI, 5-23) in patients with low levels (P = .024). The adverse effect of elevated ST2 was independent of HLA match. Moreover, high day 28 ST2 levels were associated with increased TRM with day 180 estimates of 23% (95% CI, 13-35) vs 5% (95% CI, 1-13) if levels were low (P = .001). GVHD was the most common cause of death in high ST2 patients. High concentrations of tumor necrosis factor receptor-1, interleukin-8, and regenerating islet-derived protein 3-α were also associated with TRM. Our results are consistent with those of adult donor allografts and warrant further prospective evaluation to facilitate future therapeutic intervention to ameliorate severe aGVHD and further improve survival after CBT.
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY;
Doris M
http://orcid.org/0000-0002-9422-5766
DM
Ponce
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY;
Patrick
P
Hilden
Departments of Pediatrics and Immunology, Melvin and Bren Simon Cancer Center and Wells Center for Pediatric Research, Indiana University, Indianapolis, IN; and.
Christen
C
Mumaw
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY;
Sean M
SM
Devlin
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY;
Marissa
M
Lubin
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY;
Sergio
S
Giralt
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY;
Jenna D
JD
Goldberg
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY;
Alan
A
Hanash
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY;
Katharine
K
Hsu
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY;
Robert
R
Jenq
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY;
Miguel-Angel
MA
Perales
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY;
Craig
C
Sauter
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY;
Marcel R M
MR
van den Brink
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY;
James W
JW
Young
Department of Medicine, Weill Cornell Medical College, New York, NY; Leukemia Service, Department of Medicine, and.
Renier
R
Brentjens
Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
Nancy A
NA
Kernan
Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
Susan E
SE
Prockop
Department of Medicine, Weill Cornell Medical College, New York, NY; Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
Richard J
RJ
O'Reilly
Bone Marrow Transplantation Service, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY.
Andromachi
A
Scaradavou
Departments of Pediatrics and Immunology, Melvin and Bren Simon Cancer Center and Wells Center for Pediatric Research, Indiana University, Indianapolis, IN; and.
Sophie
S
Paczesny
Adult Bone Marrow Transplantation Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; Department of Medicine, Weill Cornell Medical College, New York, NY;
Juliet N
JN
Barker
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D036101:Cord Blood Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000401:mortality; D006680:HLA Antigens / Q000378:metabolism; D019337:Hematologic Neoplasms / Q000097:blood / Q000401:mortality* / Q000628:therapy*; D006801:Humans; D007223:Infant; D000072179:Interleukin-1 Receptor-Like 1 Protein; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000097:blood*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D012189:Retrospective Studies; D013997:Time Factors; D019172:Transplantation Conditioning; D055815:Young Adult
D015415:Biomarkers; D006680:HLA Antigens; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D016209:Interleukin-8; D011956:Receptors, Cell Surface; D047888:Receptors, Tumor Necrosis Factor, Type I