TY - JOUR
T1 - Early Fever after Haploidentical Bone Marrow Transplantation Correlates with Class II HLA-Mismatching and Myeloablation but Not Outcomes
AU - McCurdy, Shannon R.
AU - Muth, Stephen T.
AU - Tsai, Hua Ling
AU - Symons, Heather J.
AU - Huff, Carol Ann
AU - Matsui, William H.
AU - Borrello, Ivan
AU - Gladstone, Douglas E.
AU - Swinnen, Lode J.
AU - Cooke, Kenneth R.
AU - Brodsky, Robert A.
AU - Bolaños-Meade, Javier
AU - Ambinder, Richard F.
AU - Varadhan, Ravi
AU - Luznik, Leo
AU - Jones, Richard J.
AU - Bettinot, Maria P.
AU - Fuchs, Ephraim J.
N1 - Publisher Copyright:
© 2018 American Society for Blood and Marrow Transplantation
PY - 2018/10
Y1 - 2018/10
N2 - Noninfectious fevers are common early after T cell–replete HLA haploidentical (haplo) peripheral blood transplants and have been associated with cytokine release syndrome and overall mortality. However, less is known regarding the incidence and associations of early fever after bone marrow transplantation (BMT) with post-transplant cyclophosphamide (PTCy). We hypothesized that early fever would be associated with myeloablative conditioning (MAC), because of its relative increase in tissue damage augmenting antigen presentation and class II HLA-mismatching because of recognition of antigen-presenting cells by CD4+ T cells. In 672 recipients of MAC HLA-matched related donor (MRD) (n = 183), MAC HLA-matched unrelated donor (MUD) (n = 115), MAC haplo (n = 79), or nonmyeloablative (NMA) haplo (n = 295) T cell–replete BMT with PTCy, we retrospectively analyzed early noninfectious fever defined as temperature of ≥38.3°C once or ≥38.0°C twice or more on days 1 to 6. Fever occurred in 13% after MAC MRD, 23% after MAC MUD, 44% after NMA haplo, and 84% after MAC haplo BMT (P <.0001). Survival outcomes did not differ between patients with and without early fever. In NMA haplo BMT, mismatch in the graft-versus-host direction at HLA-DRB1 or -DPB1 (but not HLA-A, -B, -Cw, or -DQB1) was associated with early fever compared with no mismatches at these loci (P <.0001 and P =.02, respectively). In multivariable modeling, -DRB1 or -DPB1 mismatch and higher CD3+ graft cell dose were significantly associated with early fever. Early fever is more common after haplo compared with HLA-matched BMT. Fever is associated with myeloablation, -DRB1 or -DPB1 mismatching, and higher CD3+ graft cell dose but not survival.
AB - Noninfectious fevers are common early after T cell–replete HLA haploidentical (haplo) peripheral blood transplants and have been associated with cytokine release syndrome and overall mortality. However, less is known regarding the incidence and associations of early fever after bone marrow transplantation (BMT) with post-transplant cyclophosphamide (PTCy). We hypothesized that early fever would be associated with myeloablative conditioning (MAC), because of its relative increase in tissue damage augmenting antigen presentation and class II HLA-mismatching because of recognition of antigen-presenting cells by CD4+ T cells. In 672 recipients of MAC HLA-matched related donor (MRD) (n = 183), MAC HLA-matched unrelated donor (MUD) (n = 115), MAC haplo (n = 79), or nonmyeloablative (NMA) haplo (n = 295) T cell–replete BMT with PTCy, we retrospectively analyzed early noninfectious fever defined as temperature of ≥38.3°C once or ≥38.0°C twice or more on days 1 to 6. Fever occurred in 13% after MAC MRD, 23% after MAC MUD, 44% after NMA haplo, and 84% after MAC haplo BMT (P <.0001). Survival outcomes did not differ between patients with and without early fever. In NMA haplo BMT, mismatch in the graft-versus-host direction at HLA-DRB1 or -DPB1 (but not HLA-A, -B, -Cw, or -DQB1) was associated with early fever compared with no mismatches at these loci (P <.0001 and P =.02, respectively). In multivariable modeling, -DRB1 or -DPB1 mismatch and higher CD3+ graft cell dose were significantly associated with early fever. Early fever is more common after haplo compared with HLA-matched BMT. Fever is associated with myeloablation, -DRB1 or -DPB1 mismatching, and higher CD3+ graft cell dose but not survival.
KW - HLA haploidentical
KW - HLA mismatching
KW - Post-transplant complications
KW - Post-transplant cyclophosphamide
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U2 - 10.1016/j.bbmt.2018.06.004
DO - 10.1016/j.bbmt.2018.06.004
M3 - Article
C2 - 29909152
AN - SCOPUS:85050864431
SN - 1083-8791
VL - 24
SP - 2056
EP - 2064
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 10
ER -