Improved outcomes using tacrolimus/sirolimus for graft-versus-host disease prophylaxis with a reduced-intensity conditioning regimen for allogeneic hematopoietic cell transplant as treatment of myelofibrosis.
Allogeneic hematopoietic cell transplantation (HCT) using reduced-intensity conditioning (RIC) regimens is a potentially curative treatment for patients (patients) with myelofibrosis (MF), as we and others have reported. Nonrelapse mortality (NRM) from graft-versus-host disease (GVHD) and other complications has limited the success of this approach. As part of an ongoing prospective research study at City of Hope, a combination of tacrolimus/sirolimus +/- methotrexate (MTX) for GVHD prophylaxis has become the standard treatment for our allogeneic HCT patients. In this report, we present results for 23 consecutive patients, including extended follow up for 9 patients previously reported who received cyclosporine (CsA)/mycophenolate moffetil (MMF)+/-MTX, and the current series of 14 patients who received tacrolimus/sirolimus+/-MTX, and evaluate the impact of the GVHD prophylaxis regimen on the outcomes. Median follow-up for alive patients was 29.0 months (9.5-97.0). The estimated 2-year overall survival (OS) for the CsA/MMF cohort was 55.6% (confidence interval 36.0, 71.3), and for the tacrolimus/sirolimus cohort it was 92.9% (63.3, 98.8) (P=.047). The probability of grade III or IV acute GVHD (aGVHD) was 60% for the CsA/MMF patients, and 10% for the tacrolimus/sirolimus group (P=.0102). No significant differences were seen for grade II to IV aGVHD in the 2 groups. We conclude that the combination of tacrolimus/sirolimus+/-MTX for GVHD prophylaxis in the setting of RIC HCT for MF appears to reduce the incidence of severe aGVHD and NRM, and leads to improved OS compared to CSA/MMF+/-MTX.
City of Hope Cancer Center, Department of Hematology/HCT, Duarte, California 91010, USA. dsnyder@coh.org
David S
DS
Snyder
Joycelynne
J
Palmer
Karl
K
Gaal
Anthony S
AS
Stein
Vinod
V
Pullarkat
Firoozeh
F
Sahebi
Nyana
N
Vora
Ryotaro
R
Nakamura
Stephen J
SJ
Forman
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects; D055728:Primary Myelofibrosis / Q000628:therapy*; D012720:Severity of Illness Index; D020123:Sirolimus / Q000627:therapeutic use*; D016019:Survival Analysis; D016559:Tacrolimus / Q000627:therapeutic use*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D007166:Immunosuppressive Agents; D020123:Sirolimus; D016559:Tacrolimus; D008727:Methotrexate