Graft-versus-host disease prophylaxis with everolimus and tacrolimus is associated with a high incidence of sinusoidal obstruction syndrome and microangiopathy: results of the EVTAC trial.
A calcineurin inhibitor combined with methotrexate is the standard prophylaxis for graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). Everolimus, a derivative of sirolimus, seems to mediate antileukemia effects. We report on a combination of everolimus and tacrolimus in 24 patients (median age, 62 years) with either myelodysplastic syndrome (MDS; n = 17) or acute myeloid leukemia (AML; n = 7) undergoing intensive conditioning followed by HSCT from related (n = 4) or unrelated (n = 20) donors. All patients engrafted, and only 1 patient experienced grade IV mucositis. Nine patients (37%) developed acute grade II-IV GVHD, and 11 of 17 evaluable patients (64%) developed chronic extensive GVHD. Transplantation-associated microangiopathy (TMA) occurred in 7 patients (29%), with 2 cases of acute renal failure. The study was terminated prematurely because an additional 6 patients (25%) developed sinusoidal obstruction syndrome (SOS), which was fatal in 2 cases. With a median follow-up of 26 months, the 2-year overall survival rate was 47%. Although this new combination appears to be effective as a prophylactic regimen for acute GVHD, the incidence of TMA and SOS is considerably higher than seen with other regimens.
Platzbecker
Uwe
U
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, Dresden, Germany. Uwe.Platzbecker@uniklinikum-dresden.de
von Bonin
Malte
M
Goekkurt
Eray
E
Radke
Jörgen
J
Binder
Marc
M
Kiani
Alexander
A
Stoehlmacher
Jan
J
Schetelig
Johannes
J
Thiede
Christian
C
Ehninger
Gerhard
G
Bornhäuser
Martin
M
D000328:Adult; D000368:Aged; D000743:Anemia, Hemolytic / Q000139:chemically induced*; D000068338:Everolimus; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods* / Q000401:mortality; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications / Q000628:therapy; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives*; D015996:Survival Rate; D016559:Tacrolimus / Q000009:adverse effects*; D014184:Transplantation, Homologous
D000068338:Everolimus; D020123:Sirolimus; D016559:Tacrolimus