Omission of day +11 methotrexate after allogeneic bone marrow transplantation is associated with increased risk of severe acute graft-versus-host disease.
The combination of CYA and short-course MTX is commonly used for GVHD prophylaxis after allogeneic BMT. Severe mucositis and organ dysfunction early after transplantation often lead to omission of the day +11 dose of MTX. To examine whether this omission increases the risk of acute or chronic GVHD, we reviewed 135 allogeneic BMTs performed at our institution in which CYA and short-course MTX prophylaxis were used. Patients receiving less than three doses of MTX and those who died before day +11 were excluded. Of the 123 eligible patients, 84 received all four doses and 39 received three doses, with the fourth dose withheld because of severe mucositis (n = 27) or hepatic or renal dysfunction (n = 12). Acute GVHD of any grade developed in 23 patients (59%) in the three-dose group compared with 57 patients (68%) in the four-dose group (P = 0.33). Chronic GVHD developed in 15 patients (38%) in the three-dose group compared with 31 patients (37%) in the four-dose group (P = 0.87). There was no difference in the overall rate of acute or chronic GVHD between the groups. However, the three-dose group was more likely to develop grade III or IV acute GVHD (12 of 39 (31%) ) compared with the four-dose group (12 of 84 (14%); P = 0.03). Relapse-free survival was similar for the two groups. We conclude that omitting day +11 MTX appears to increase the risk of severe acute GVHD.
Kumar
S
S
Division of Hematology and Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Wolf
R C
RC
Chen
M G
MG
Gastineau
D A
DA
Gertz
M A
MA
Inwards
D J
DJ
Lacy
M Q
MQ
Tefferi
A
A
Litzow
M R
MR
D000208:Acute Disease; D000328:Adult; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000401:mortality; D002648:Child; D004334:Drug Administration Schedule; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000209:etiology* / Q000517:prevention & control; D006402:Hematologic Diseases / Q000150:complications / Q000401:mortality / Q000628:therapy; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D012008:Recurrence; D012189:Retrospective Studies; D012306:Risk; D016019:Survival Analysis; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000401:mortality; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D008727:Methotrexate