A randomized trial comparing use of cyclosporin and methotrexate for graft-versus-host disease prophylaxis in bone marrow transplant recipients with haematological malignancies.
Patients with haematological malignancies with HLA-identical marrow donors were randomized to treatment with cyclosporin (CSA) or methotrexate (MTX). Two of the 29 patients randomized to MTX died before engraftment compared with none of the 30 treated with CSA. Engraftment by leucocytes (P less than 0.0001), granulocytes (P less than 0.02), and reticulocytes (P less than 0.01) was faster among the CSA patients. There were no significant differences between the two groups regarding transfusions, hospitalization and incidence of early septicaemia. Granulocyte transfusions were required in seven of 29 MTX and two of 30 CSA patients (not significant: NS). Overall (grade I-IV) acute graft-versus-host disease (GVHD) was more common (P = 0.001) in the CSA patients. Grade II-IV acute GVHD was seen in 40% of the CSA patients compared with 22% in the MTX patients (NS). In the adult patients grade II-IV GVHD was slightly more common (P less than 0.05) in those treated with CSA compared with MTX. Chronic GVHD appeared in 30 and 39% in the two groups respectively. Actuarial 3-year survival was 58% for the CSA patients and 69% for the MTX patients. There were no significant differences regarding the incidence of interstitial pneumonitis or relapses between the two groups. The side-effects of CSA treatment includes nephrotoxicity (83%), hepatotoxicity (20%), hirsutism (43%), hypertension (23%), tremor (27%) and gingival hyperplasia (27%). Serum creatinine values were increased at 3 and 6 months in the CSA group but were within the normal range after 6 months. A blind study on oral side-effects revealed that CSA patients more often had a normal mucosa (P = 0.025) and less frequently had mucositis (P = 0.01) compared with the MTX group.
Ringdén
O
O
Department of Transplantation Surgery, Karolinska Institute, Stockholm, Sweden.
Bäckman
L
L
Lönnqvist
B
B
Heimdahl
A
A
Lindholm
A
A
Bolme
P
P
Gahrton
G
G
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation; D002648:Child; D002675:Child, Preschool; D002986:Clinical Trials as Topic; D003524:Cyclosporins / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D006801:Humans; D007938:Leukemia / Q000150:complications / Q000401:mortality / Q000628:therapy*; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009059:Mouth Diseases / Q000209:etiology; D011897:Random Allocation; D012008:Recurrence
D003524:Cyclosporins; D008727:Methotrexate