Prophylaxis for acute graft-versus-host disease following unrelated donor bone marrow transplantation
Phillips, G.L.; Nevill, T.J.; Spinelli, J.J.; Nantel, S.H.; Klingemann, H.G.; Barnett, M.J.; Shepherd, J.D.; Chan, K.W.; Meharchand, J.M.; Sutherland, H.J.
Bone Marrow Transplantation 15(2): 213-219
1995
ISSN/ISBN: 0268-3369 PMID: 7539667 Document Number: 440970
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 gt 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 gtoreq II (probability, 58% (95% CI 41-76%)); 7 had grade gtoreq 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. Event-free survival (EFS) is 46% (95% CI 27-63%) at 3 yrs, with a median followup of 33 mos (range 19-42) in survivors. This regimen may diminish the severity of acute GVHD without a high incidence of graft rejection. The relatively low relapse rate observed to date suggests the persistence of an allogeneic antitumor effect. These preliminary results require confirmation.