Thalidomide after allogeneic haematopoietic stem cell transplantation: activity in chronic but not in acute graft-versus-host disease.
Thalidomide was used to treat acute (n=21) or chronic (n=59) graft-vs-host disease (GVHD) in 80 haematopoietic stem cell allograft recipients after failure to respond to the combination of cyclosporine and corticosteroids with or without other agents. The median time to onset of acute GVHD was 11 days, and thalidomide was started at a median of 48 days post transplant. In addition to corticosteroids and cyclosporine, 13 patients had also received other agents before thalidomide. None of the patients responded and all died of acute GVHD. For chronic GVHD (limited in 13, extensive in 46), thalidomide was started at a median of 385 days post transplant. In addition to corticosteroids and cyclosporine, 34 patients received azathioprine concomitantly. In all patients, thalidomide was added to the ongoing immunosuppressive regimen. The median duration of therapy with thalidomide was 60 days (range, 11-1210; <2 weeks in 11). In total, 13 patients (22%) had complete response, eight (14%) partial response and 38 (64%) no response. Response rates were comparable for limited (39%) and extensive (33%) chronic GVHD. At a median of 53 months, 19 patients are alive, 13 without evidence of chronic GVHD. Survival was significantly better in patients who responded to thalidomide. The principal causes of death were progressive chronic GVHD (n=29) and relapsed leukaemia (n=7). In conclusion, thalidomide has no activity in acute GVHD, but has some activity in chronic GVHD in combination with other agents.
Kulkarni
S
S
Leukaemia and Myeloma Units, The Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, UK.
Powles
R
R
Sirohi
B
B
Treleaven
J
J
Saso
R
R
Horton
C
C
Atra
A
A
Ortin
M
M
Rudin
C
C
Goyal
S
S
Sankpal
S
S
Meller
S
S
Pinkerton
C R
CR
Mehta
J
J
Singhal
S
S
D000208:Acute Disease; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000401:mortality; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D016019:Survival Analysis; D013792:Thalidomide / Q000627:therapeutic use*; D014184:Transplantation, Homologous
D000305:Adrenal Cortex Hormones; D013792:Thalidomide; D016572:Cyclosporine