TY - JOUR
T1 - Grade II Acute Graft-versus-Host Disease and Higher Nucleated Cell Graft Dose Improve Progression-Free Survival after HLA-Haploidentical Transplant with Post-Transplant Cyclophosphamide
AU - McCurdy, Shannon R.
AU - Kanakry, Christopher G.
AU - Tsai, Hua Ling
AU - Kasamon, Yvette L.
AU - Showel, Margaret M.
AU - Bolaños-Meade, Javier
AU - Huff, Carol Ann
AU - Borrello, Ivan
AU - Matsui, William H.
AU - Brodsky, Robert A.
AU - Ambinder, Richard F.
AU - Bettinotti, Maria P.
AU - Fuchs, Ephraim J.
AU - Rosner, Gary L.
AU - Jones, Richard J.
AU - Luznik, Leo
N1 - Publisher Copyright:
© 2017 The American Society for Blood and Marrow Transplantation
PY - 2018/2
Y1 - 2018/2
N2 - Compared with standard graft-versus-host disease (GVHD) prophylaxis platforms, post-transplantation cyclophosphamide (PTCy) after T cell–replete HLA-haploidentical (haplo) bone marrow transplantation (BMT) reduces the risk of grades III to IV acute (a) and chronic (c) GVHD, but maintains similar rates of grade II aGVHD. Given that mild GVHD has been associated with reduced treatment failure in HLA-matched BMT, we evaluated the risk factors for and effects of GVHD on survival in 340 adults with hematologic malignancies who engrafted after nonmyeloablative haplo-BMT with PTCy, mycophenolate mofetil, and tacrolimus. The cumulative incidence at 100 days of grade II and grades III to IV aGVHD were 30% (95% confidence interval [CI], 25% to 35%) and 2% (95% CI, 1% to 4%), respectively. The 1-year cumulative incidence of cGVHD was 10% (95% CI, 7% to 13%). In landmark analyses at 100 days, the 4-year probabilities of overall survival (OS) and progression-free survival (PFS) were, 48% (95% CI, 41% to 56%) and 39% (95% CI, 32% to 47%) for patients without grades II to IV aGVHD, compared with 63% (95% CI, 53% to 73%) and 59% (95% CI, 50% to 71%) for patients with grade II aGVHD (P =.05 and P =.009). In multivariable modeling, when compared with patients who never experienced GVHD, the hazard ratio (HR) for OS and PFS in patients with grade II aGVHD was.78 (95% CI,.54 to 1.13; P =.19) and.69 (95% CI,.48 to.98; P =.04). Higher nucleated cell graft dose was also associated with improved OS (HR,.88; 95% CI,.78 to 1.00; P =.05) and PFS (HR,.89; 95% CI,.79 to 1.0; P =.05) and decreased risk of grades III to IV aGVHD (subdistribution HR,.66; 95% CI,.46 to.96; P =.03). PTCy reduces grades III to IV aGVHD and cGVHD, but retains similar incidence of grade II aGVHD, the development of which improves PFS. Higher nucleated cell graft dose goals may also improve survival after nonmyeloablative haplo-BMT with PTCy.
AB - Compared with standard graft-versus-host disease (GVHD) prophylaxis platforms, post-transplantation cyclophosphamide (PTCy) after T cell–replete HLA-haploidentical (haplo) bone marrow transplantation (BMT) reduces the risk of grades III to IV acute (a) and chronic (c) GVHD, but maintains similar rates of grade II aGVHD. Given that mild GVHD has been associated with reduced treatment failure in HLA-matched BMT, we evaluated the risk factors for and effects of GVHD on survival in 340 adults with hematologic malignancies who engrafted after nonmyeloablative haplo-BMT with PTCy, mycophenolate mofetil, and tacrolimus. The cumulative incidence at 100 days of grade II and grades III to IV aGVHD were 30% (95% confidence interval [CI], 25% to 35%) and 2% (95% CI, 1% to 4%), respectively. The 1-year cumulative incidence of cGVHD was 10% (95% CI, 7% to 13%). In landmark analyses at 100 days, the 4-year probabilities of overall survival (OS) and progression-free survival (PFS) were, 48% (95% CI, 41% to 56%) and 39% (95% CI, 32% to 47%) for patients without grades II to IV aGVHD, compared with 63% (95% CI, 53% to 73%) and 59% (95% CI, 50% to 71%) for patients with grade II aGVHD (P =.05 and P =.009). In multivariable modeling, when compared with patients who never experienced GVHD, the hazard ratio (HR) for OS and PFS in patients with grade II aGVHD was.78 (95% CI,.54 to 1.13; P =.19) and.69 (95% CI,.48 to.98; P =.04). Higher nucleated cell graft dose was also associated with improved OS (HR,.88; 95% CI,.78 to 1.00; P =.05) and PFS (HR,.89; 95% CI,.79 to 1.0; P =.05) and decreased risk of grades III to IV aGVHD (subdistribution HR,.66; 95% CI,.46 to.96; P =.03). PTCy reduces grades III to IV aGVHD and cGVHD, but retains similar incidence of grade II aGVHD, the development of which improves PFS. Higher nucleated cell graft dose goals may also improve survival after nonmyeloablative haplo-BMT with PTCy.
KW - Bone marrow transplantation
KW - Cyclophosphamide
KW - Graft dose
KW - Graft-versus-host disease
KW - HLA-haploidentical
UR - http://www.scopus.com/inward/record.url?scp=85037029493&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85037029493&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2017.10.023
DO - 10.1016/j.bbmt.2017.10.023
M3 - Article
C2 - 29055682
AN - SCOPUS:85037029493
SN - 1083-8791
VL - 24
SP - 343
EP - 352
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 2
ER -