ABSTRACT
Objective To observe the effect of bortezomib on acute graft-versus-host disease (aGVHD) in an aGVHD model of mice and investigate the related mechanism. Methods Male C57BL/6( H-2Kb)mice were used as donors and female Balb/c (H-2Kd) mice used as recipients. Balb/c mice received total body irradiation (TBI) by 7.0 Gy X-radiation, and randomly divided into five groups. normal (group A), TBI (group B), TBI + bortezomib (group C), TBI + bone marrow cells (BMC) + spleen cells (SC) (group D) and TBI + bortezomib + BMC + SC (group E). The physical signs and the pathological damage of aGVHD, mean survival time, and chimerism were observed in recipients. The NF-κB p65 levels in nuclei of the liver and small intestine tissues of groups A,B and C were analyzed by Western blot. Results ( 1 ) The clinical aGVHD score in group D was (7.37±0. 32), significantly higher than in group E (5.85 ± 0.40) (P＜0. 05). Histopathology of the gut, liver and skin illuminated that the Ⅲ-Ⅳ degree GVHD occurred in group D. The occurrence of aGVHD in group E was later than in group D. The symptoms and the pathological damage of aGVHD in group E were milder than in group D. The average survival time in group E was significantly longer than that in group D (P＜0.05). The percentage of donor-derived cells in recipient mice was above 90% at day 12 after transplantation; (2) NF-κB p65 levels in nuclei of the liver and small intestine tissues in group B was significantly higher than in group C on the day 1,3 and 5 (P＜0. 05). Conclusion Bortezomib can inhibit the activation and expression of NF-κB,which may be the underlying mechanism for it to relieve aGVHD.
ABSTRACT
Objective To analyze the outcome and prognosis-related factors of MA (mitoxantrone+cytarabine) regimen for acute myeloid leukemia(AML). Methods 102 untreated AML patients were treated with MA. All patients were divided into two groups according to age, blood white cell count(WBC), FrenchAmerican-British (FAB) morphology, level of lactate dehydrogenase (LDH) and immunophynotype respectively.Analyze the prognosis-related factors. Results The complete remission (CR), partial remission (PR), nonresponse (NR) rate, and remission rate (CR+PR) of all the 102 cases were 63.73 % (65/102), 17.65 % (18/102), 18.62 % (419/102)and 81.38 % (83/102) respectively. The patients younger than 60 years old, WBC＜100×109/L, LDH≤600 U/L, FAB-M2 morphology group had higher CR and remission rate. The CR rate of patients with CD7 positive had statistical difference from that of patients with CD7 negative (P ＜0.05), but the remission rate not. However, the CR and remission rate of patients with CD19 positive had no statistical difference from that of patients with CD19 negative (P ＞0.05). Conclusion These results suggest that use of MA regimen was effective and safe for AML. Age, WBC, FAB morphology, level of LDH and CD7 expression are prognosis-related factors for clinical outcome.