Methotrexate combined with cyclosporin A decreases graft-versus-host disease, but increases leukemic relapse compared to monotherapy.
Forty patients with leukemia receiving HLA-identical sibling marrow and treated with four doses of methotrexate (MTX) in combination with cyclosporin A (CSA) for prevention of graft-versus-host disease (GVHD) were compared with retrospective controls consisting of 57 patients treated with MTX alone and 30 patients treated with CSA alone. Follow-up time ranged from 2.6 to 6.7 years after bone marrow transplantation. Patients in the MTX + CSA group were older and received a smaller marrow cell dose, but were otherwise comparable regarding disease status, donor/recipient sex match and seropositivity for cytomegalovirus (CMV) and other herpes viruses. Engraftment was slowest in the MTX + CSA group and fastest in the CSA group (p = 0.005 vs MTX and p less than 0.001 vs CSA). The incidence of moderate to severe acute GVHD (grade II-IV) was 8% among patients on MTX + CSA and 26% and 47% in the MTX (p = 0.028) and CSA (p = 0.0001) groups respectively. The corresponding figures for chronic GVHD were 25, 42 and 40% (n.s.). The incidence of CMV interstitial pneumonia was 0% in patients treated with MTX + CSA compared to 23% in the MTX treated patients (p = 0.01) and 11% in the CSA treated patients (p = 0.05). The actuarial 3-year survival in the three groups was similar, 56% for the MTX + CSA patients and 53% for both the MTX and CSA patients (n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)
Aschan
J
J
Department of Transplantation Surgery, Karolinska Institute, Huddinge Hospital, Stockholm, Sweden.
Ringdén
O
O
Sundberg
B
B
Gahrton
G
G
Ljungman
P
P
Winiarski
J
J
D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D003524:Cyclosporins / Q000008:administration & dosage* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D007938:Leukemia / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D012189:Retrospective Studies; D013997:Time Factors
D003524:Cyclosporins; D008727:Methotrexate