Korean J Hematol.  2006 Jun;41(2):73-82. 10.5045/kjh.2006.41.2.73.

Impact of Day +11 Methotrexate on the Incidence of Graft-versus-host Disease after HLA-identical Allogeneic Peripheral Blood Stem Cell Transplantation

• Ahn BM
• Jung YR
• Lee KB
• Sohn SK
• Kim JG
• Baek JH
• Cho YY
• Chae YS
• Jeon SB
• Moon JH
• Kim SN
• Lee SJ
• Suh JS
• Lee KS

• KMID: 2083480
• DOI: http://doi.org/10.5045/kjh.2006.41.2.73

Abstract

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.

Keyword

Methotrexate; Graft-versus-host disease; Allogeneic peripheral blood stem cell transplantation

MeSH Terms

Cyclosporine
Graft vs Host Disease*
Humans
Incidence*
Methotrexate*
Mucositis
Multivariate Analysis
Peripheral Blood Stem Cell Transplantation*
Recurrence
Renal Insufficiency
Cyclosporine
Methotrexate

Figure

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  Fig. 1 The cumulative incidence of acute and chronic GVHD after HLA-identical allogeneic PBSCT (n=68). The group with 4 doses of methotrexate showed significantly lower incidence of acute GVHD (A), grade III-IV acute GVHD (B), overall chronic GVHD (C), and extensive chronic GVHD (D).

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