Prophylaxis for acute graft-versus-host disease following unrelated donor bone marrow transplantation.
Despite the use of conventional chemoprophylaxis regimens, patients receiving unrelated-donor BMT are at high risk of developing severe acute GVHD. We evaluated a prophylactic regimen combining CsA, MTX and anti-CD5-ricin A chain immunotoxin (H65-RTA) in 31 patients; pentoxifylline was also given to reduce the anticipated nephrotoxicity of CsA. In most cases, planned doses of CsA, MTX and H65-RTA were given (i.e. to 77%, 77% and 93% of patients, respectively). Although fluid retention requiring diuretic therapy was frequent, only 1 patient had a > 10% unexplained increase in body weight during the first 21 days post-BMT. Also, while significant increase of the baseline serum creatinine was noted in 7 patients, none required dialysis. One patient suffered a reversible allergic reaction to the immunotoxin; no other side effects attributable to this regimen were observed. All but 2 patients engrafted (1 died of fungemia on d + 19 and the other had persistent leukemia) and no late graft failures were observed. Seventeen patients developed acute GVHD grade > or = II (probability, 58% [95% CI 41-76%]); 7 had grade > or = III (probability, 24% [95% CI 12-43%]). In the 27 patients who achieved stable engraftment and have survived beyond d + 100, the 3-year probability of developing chronic GVHD was 66% (95% CI 48-84%). As of the last follow-up prior to 01 May 1994, 13 patients are alive in CR and one in relapse; 9 of these patients are off all immunosuppressives and well. Four other patients relapsed and died, and 13 died of other transplant-related causes.(ABSTRACT TRUNCATED AT 250 WORDS)
Phillips
G L
GL
Leukemia/Bone Marrow Transplantation Program of British Columbia, Vancouver Hospital and Health Sciences Centre, Canada.
Nevill
T J
TJ
Spinelli
J J
JJ
Nantel
S H
SH
Klingemann
H G
HG
Barnett
M J
MJ
Shepherd
J D
JD
Chan
K W
KW
Meharchand
J M
JM
Sutherland
H J
HJ
D000293:Adolescent; D000328:Adult; D015703:Antigens, CD / Q000276:immunology; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D018956:CD5 Antigens; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006650:Histocompatibility Testing; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage*; D007223:Infant; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged
D015703:Antigens, CD; D018956:CD5 Antigens; D000922:Immunotoxins; D016572:Cyclosporine; D008775:Methylprednisolone