ABSTRACT
OBJECTIVE: To analyze the incidence and the effective prevention and treatment of graft-versus-host disease (GVHD) for the allogeneic peripheral blood stem cell transplantation (allo-PBSCT) for the treatment of leukemia. METHODS: Fifty patients with acute leukemia (n = 29) and chronic myeloid leukemia (n = 21) were treated with allo-PBSCT. The conditioning regimens were TBI plus CTX and Vp16 or TBI plus CTX. Two regimens were used for prophylaxis of GVHD: one was the combination of low dose cyclosporine (CsA, 2 - 3 mg x kg(-1) x d(-)1 i.v. or 4 - 6 mg x kg(-1) x d(-1) p.o.) and short course methotrexate (MTX, 15 approximately 10 mg, +1, +3, +6, +11 d) (CsA/MTX group, 32 patients), the other was short course of mycophenolate mofetil (MMF, 1.0 bid, +1 - +28 d) in addition to CsA and MTX (MMF/CsA/MTX group, 18 patients). RESULTS: All patients were successfully engrafted and the median times to ANC > 0.5 x 10(9)/L and to platelet > 20 x 10(9)/L were 14 (10 - 22) and 20 (10 - 68) days post PBSCT respectively. The incidence of acute GVHD (aGVHD) was 40% (20/50) and of grade III - IV was 12% (6/50). The chronic GVHD (cGVHD) occurred in 22 out of 33 (66.7%) evaluable patients (survived longer than 6 months post PBSCT) and extensive cGVHD in 11 out of 33 (33.3%) patients. Patients with aGVHD displayed significantly higher sIL-2R levels [(277.3 +/- 26.4) U/L] and CD(25)(+) cells [(8.1 +/- 3.4)%] than those without GVHD [(128.1 +/- 96.7) U/L and (3.6 +/- 1.7)%] (P < 0.05). The incidences of aGVHD (16.7%) and extensive cGVHD (9.1%) in MMF/CsA/MTX group were significantly lower than that in CsA/MTX group (53.1% and 45.5%, P < 0.05). The median follow-up duration was 30 (3 - 70) months and 33 patients were still alive. The relapse rate was significantly higher in GVHD negative group (47.1%) than in GVHD positive group (0, P < 0.05). The 3 year disease-free-survival (DFS) rate was 66%. CONCLUSION: The incidence of aGVHD was low, but of cGVHD was high in allo-PBSCT. sIL-2R and CD(25)(+) cells after PBSCT may provide predictive markers for aGVHD. The MMF/CsA/MTX regimen for prevention of aGVHD in allo-PBSCT is more effective than the CsA/MTX one. There was a strong antileukemic effect of GVHD in the allo-PBSCT.
Subject(s)
Graft vs Host Disease/prevention & control , Leukemia/therapy , Mycophenolic Acid/analogs & derivatives , Peripheral Blood Stem Cell Transplantation/adverse effects , Adolescent , Adult , Cyclosporine/therapeutic use , Drug Therapy, Combination , Enzyme Inhibitors/therapeutic use , Female , Graft vs Host Disease/etiology , Humans , Immunosuppressive Agents/therapeutic use , Male , Methotrexate/therapeutic use , Middle Aged , Mycophenolic Acid/therapeutic use , Peripheral Blood Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Transplantation, Homologous/adverse effectsABSTRACT
To investigate the relationship between interleukin-18 (IL-18) and human acute graft-versus-host disease (aGVHD), 26 patients undergoing allogeneic peripheral blood stem cell transplantation (allo-PBSCT) were included in this study. IL-18 secreted by peripheral blood mononuclear cells (MNCs) was measured by enzyme-linked immunosorbent assay (ELISA) before transplantation and during aGVHD. The results showed that grade I GVHD and grades III-IV GVHD developed in 10 and 5 cases, respectively. The levels in the supernatants of MNCs from patients with aGVHD were significantly higher than those in the cases without aGVHD. The levels of IL-18 were correlated with the severity of aGVHD. It is concluded that IL-18 plays an important role in the development of aGVHD.
