Clinical Factors Predicting the Response of Acute Graft-versus-Host Disease to Corticosteroid Therapy: An Analysis from the GVHD Working Group of the Japan Society for Hematopoietic Cell Transplantation

Abstract

Systemic corticosteroid therapy is recommended as a first-line treatment for acute graft-versus-host disease (GVHD). We performed a retrospective study to identify the factors affecting the response of grade II to IV acute GVHD to systemic corticosteroid therapy using the Japanese national registry data for patients who received first allogeneic hematopoietic cell transplantation with bone marrow (BM) (n ¼ 1955), peripheral blood stem cells (PBSCs) (n ¼ 642), or umbilical cord blood (UCB) (n ¼ 839). Of 3436 patients, 2190 (63.7%) showed improvement of acute GVHD to first-line therapy with corticosteroids. Various factors were identified to predict corticosteroid response. Interestingly, UCB (versus HLA-matched related BM) transplantation was significantly associated with a higher probability of improvement, whereas HLA-matched unrelated BM and HLA-mismatched stem cell sources other than UCB were significantly associated with a lower probability of improvement. HLA-matched related PBSC transplantation was not significantly different from HLA-matched related BM transplantation. Patients without improvement from corticosteroid therapy had a 2.5-times higher nonrelapse mortality and a .6-times lower overall survival rate. The present study demonstrated, for the first time, a higher probability of improvement in grade II to IV acute GVHD with systemic corticosteroid therapy in patients after UCB transplantation than in those after BM and PBSC transplantation. A prospective study is warranted.

Comparison of transplant outcomes from matched sibling bone marrow or peripheral blood stem cell and unrelated cord blood in patients 50 years or older

“…Although the reason for this remains unclear, our data showed GVHD was not a common cause of early death after CBT. Murata et al reported a higher response of Grades II-IV acute GVHD to systemic corticosteroid treatment in CBT recipients than in BMT and PBSCT recipients [47], suggesting that the higher incidence of severe acute GVHD might not have contributed to the higher early TRM after CBT in our study. On the other hand, chronic GVHD was a less common cause of late death after CBT compared with BMT and PBSCT in our study.…”

Impact of pretransplant body mass index on the clinical outcome after allogeneic hematopoietic SCT

“…One possible reason why obese patients had a higher risk of GVHD-related death is the higher incidences of hepatic and gut acute GVHD in comparison with patients with normal BMI, which have been reported to be associated with a poor response to GVHD therapy and an increased risk of NRM. [13][14][15][16] One hypothesis is that the greater tissue damage caused by the higher dose of chemotherapy in obese patients may contribute to the induction of cytokine storms, which leads to severe acute GVHD. 17 Another hypothesis is that the different immune status in obesity affects the functional status of immune cells after allogeneic HSCT.…”

“…Considering the mortality associated with hepatic acute GVHD, we should intervene to reduce the risk of hepatic acute GVHD in obese patients. [13][14][15][16] It is well-known that a prominent obesity-induced immune shift in the liver, so-called non-alcoholic steatohepatitis, causes inflammation in the liver, which might contribute to the subsequent increased risk of hepatic acute GVHD. 18,24 Practically, careful monitoring and early institution of high-dose immunosuppression are suggested.…”

Prophylactic and therapeutic treatment of graft-versus-host disease in Japan

“…A nationwide study revealed that the response rate of grade II-IV acute GVHD to systemic PSL or mPSL in Japanese patients was approximately 64 % [122], which is comparable to that in Caucasian patients [123,124]. Patients without improvement from initial therapy with systemic corticosteroid had a 2.5-times higher non-relapse mortality and a 0.6-times lower overall survival rate [122]. A higher probability of improvement was obtained in patients after CBT (vs. HLA-matched related BMT).…”

“…If systemic steroid therapy is ineffective, Japanese patients, as well as Western populations, cannot achieve a satisfactory survival rate [122]. We have to pay attention to acute GVHD, especially in elderly patients, because the hazard ratio for non-relapse mortality in patients 50 years or older is twice as great as that of 20-year-old patients [139].…”