Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Biostatistics & Bioinformatics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland.
Biol Blood Marrow Transplant. 2018 Oct;24(10):2056-2064. doi: 10.1016/j.bbmt.2018.06.004. Epub 2018 Jun 15.
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.
非传染性发热在 T 细胞完全重建的 HLA 单倍体（haplo）外周血移植后很常见，与细胞因子释放综合征和总死亡率有关。然而，对于骨髓移植（BMT）后早期发热与 post-transplant cyclophosphamide（PTCy）的关系知之甚少。我们假设早期发热与骨髓清除性条件（MAC）有关，因为其相对增加了组织损伤，从而增强了抗原呈递，并且由于 CD4 T 细胞识别抗原呈递细胞，HLA 错配 II 类增加。在 672 名接受 MAC HLA 匹配的亲缘供体（MRD）（n=183）、MAC HLA 匹配的无关供体（MUD）（n=115）、MAC haplo（n=79）或非骨髓清除性（NMA）haplo（n=295）T 细胞重建 BMT 并接受 PTCy 的患者中，我们回顾性分析了早期定义为 1 至 6 天内体温≥38.3°C 一次或≥38.0°C 两次或更多的非传染性发热。MAC MRD 后发热发生率为 13%，MAC MUD 后为 23%，NMA haplo 后为 44%，MAC haplo BMT 后为 84%（P<.0001）。有早期发热和无早期发热的患者生存结局无差异。在 NMA haplo BMT 中，与这些位点无错配相比，HLA-DRB1 或-DPB1（但不是 HLA-A、-B、-Cw 或-DQB1）移植物抗宿主错配与早期发热相关（分别为 P<.0001 和 P=0.02）。在多变量模型中，-DRB1 或-DPB1 错配和较高的 CD3 移植物细胞剂量与早期发热显著相关。与 HLA 匹配的 BMT 相比，haplo 后更常见早期发热。发热与骨髓清除、-DRB1 或-DPB1 错配、较高的 CD3 移植物细胞剂量有关，但与生存无关。
