Association of three cytokines with graft versus host disease after allogeneic hematopoietic stem cell transplantation for leukemia / 中国组织工程研究

ABSTRACT

BACKGROUND: Recently, a few studies have reported the correlation between transforming growth factor-α (TGF-α) and graft-versus-host disease (GVHD); however, the combination of TGF-α with other cytokines in patients with chronic or acute GVHD requires further study.OBJECTIVE: To analyze the changes of serum tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and transforming growth factor-α (TGF-α) in leukemic patients after allogeneic hematopoietic stem cell transplantation (Allo-HSCT) and investigate the effects of these cytokines on different grades of GVHD.DESIGN: Case control study.SETTING: Department of Hematology, Organ Transplantation Center, the Second Affiliated Hospital, General Hospital of Chinese PLA; Department of Nuclear Medicine, the Second Affiliated Hospital, General Hospital of Chinese PLA.PARTICIPANTS: Forty-two leukemic patients (23 males and 19 females, 16-68 years old, mean age of 35 years) who underwent Allo-HSCT for the first time were selected from the Department of Hematology, Organ Transplantation Center, the Second Affiliated Hospital, General Hospital of Chinese PLA and Department of Transplantation, the 307 Hospital of Chinese PLA from June 2005 to June 2007. Twelve patients had acute granulocytic leukemia (AGL), fifteen patients had acute lymphocytic leukemia (ALL), and fifteen patients had chronic granulocytic leukemia (CGL). Among the 42 patients, 37 underwent peripheral blood transplantation and five received bone marrow transplantation. Twenty-one patients had acute GVHD (18 cases in grades Ⅰ-Ⅱ and three cases in grades Ⅲ-Ⅳ) after Allo-HSCT, but the other 21 patients did not. Fourteen patients had chronic GVHD (five cases of limited type and nine cases of extensive type), but the other 28 patients did not. An additional 30 healthy subjects (18 males and 12 females, 20-70 years old, mean age of 44 years) were collected as a normal control group. All patients provided confirmed consent, and the study was approved by the local ethics committee.METHODS: Levels of serum TNF-α, IL-4, and TGF-α in leukemic patients with Allo-HSCT and normal subjects were measured by radio-immuno-assay, the cytokines levels of the patients with/without acute GVHD, of those with/without chronic GVHD and of different grades of GVHD were compared.MAIN OUTCOME MEASURES: Comparisons of serum TNF-α, IL-4, and TGF-α among the groups.RESULTS: All 42 leukemic patients and 30 healthy subjects were included in the final analysis. Levels of TNF-α, IL-4, and TGF-α in patients with acute or chronic GVHD were significantly higher than those in the normal subjects (P<0.05-0.01). Levels of TNF-α and IL-4 in patients without acute GVHD were significantly higher than those in the normal subjects (P<0.01,0.05). Levels of TNF-α, IL-4, and TGF-α in patients with acute GVHD were significantly higher than those in patients without acute GVHD (P<0.05). Levels of TNF-α, IL-4, and TGF-α in patients with chronic GVHD were significantly higher than those in patients without chronic GVHD (P<0.05). Levels of serum TNF-α and TGF-α in patients with acute GVHD of grades Ⅲ-Ⅳ or chronic GVHD of extensive type were significantly higher than those in patients with acute GVHD of grades Ⅰ-Ⅱ or chronic GVHD of limited type (P<0.05-0.01).CONCLUSION: After Allo-HSCT, dynamically monitoring changes of levels of TNF-α, IL-4, and TGF-α may serve as a possible means of predicting the onset of acute or chronic GVHD and may contribute considerably to deciding clinical severity of GVHD.