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KMID : 0366220060410020073
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Korean Journal of Hematology
2006 Volume.41 No. 2 p.73 ~ p.82
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Impact of Day +11 Methotrexate on the Incidence of Graft-versus-host Disease after HLA-identical Allogeneic Peripheral Blood Stem Cell Transplantation
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Ahn Byung-Min
Jung Yee-Ryong
Lee Kyu-Bo
Sohn Sang-Kyun
Kim Jong-Gwang
Baek Jin-Ho
Cho Yoon-Young
Chae Yee-Soo
Jeon Seok-Bong
Moon Joon-Ho
Kim Shi-Nae
Lee Soo-Jung
Suh Jang-Soo
Lee Kun-Soo
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Abstract
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Background: Cyclosporine (CSA) plus 4 doses of methotrexate (MTX) is the commonly used regimen for GVHD prophylaxis. It has been previously found that the omission of the day +11 dose of MTX was associated with an increased risk of acute GVHD in the allogeneic BMT setting. However, little is known about its impact in the PBSCT setting.
Methods: Of the 68 patients, 30 patients (44%) received 4 doses of MTX (the MTX4 group), while 38 patients (56%) received less than 4 doses (the MTX3 group) because of their severe mucositis, hepatic dysfunction or renal failure.
Results: The cumulative incidence of acute GVHD was 60% in the MTX4 and 86% in the MTX3 group (P=0.038), while that of grade III and IV acute GVHD was 7% in the MTX4 group and 39% in the MTX3 group (P=0.017). Of the 61 patients evaluated for chronic GVHD, the cumulative incidence of chronic GVHD was 54% in the MTX4 group and 97% in the MTX3 group (P=0.001), while that of extensive chronic GVHD was 26% in the MTX4 group and 63% in the MTX3 group (P=0.004). There were no differences in the overall survival and the incidence of relapse between the two groups. On multivariate analyses, MTX3 was a poor prognostic factor in terms of acute GVHD and extensive chronic GVHD.
Conclusion: This study suggested that omitting day +11 MTX and the clinical situation of the MTX3 group seemed to be associated with an increased incidence of acute and chronic GVHD. Accordingly, administration of day +11 MTX accompanied by active treatment of mucositis may prevent GVHD in the allogeneic PBSCT setting, but we need to conduct a large scale prospective study.
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KEYWORD
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Methotrexate, Graft-versus-host disease, Allogeneic peripheral blood stem cell transplantation
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