TY - JOUR
T1 - Extended Mycophenolate Mofetil and Shortened Cyclosporine Failed to Reduce Graft-versus-Host Disease after Unrelated Hematopoietic Cell Transplantation with Nonmyeloablative Conditioning
AU - Baron, Frédéric
AU - Sandmaier, Brenda M.
AU - Storer, Barry E.
AU - Maris, Michael B.
AU - Langston, Amelia A.
AU - Lange, Thoralf
AU - Petersdorf, Effie
AU - Bethge, Wolfgang
AU - Maziarz, Richard T.
AU - McSweeney, Peter A.
AU - Pulsipher, Michael A.
AU - Wade, James C.
AU - Chauncey, Thomas R.
AU - Shizuru, Judith A.
AU - Sorror, Mohamed L.
AU - Woolfrey, Ann E.
AU - Maloney, David G.
AU - Storb, Rainer
N1 - Funding Information:
This work was supported in part by grants CA78902, CA92058, CA18029, CA49605, HL36444, CA15704, and HL088021 from the National Institutes of Health, Department of Health and Human Services (DHHS), Bethesda, MD. R.S. also received support from the Laura Landro Salomon Endowment Fund. M.S. received support from the Paros Family Fund. F.B. is a research associate of the National Fund for Scientific Research (FNRS) Belgium. The authors wish to thank the data coordinators Heather Hildebrandt and Debbie Bassuk, and the study nurses, Mary Hinds, John Sedgwick, and Michelle Bouvier, for their invaluable help in making the study possible. The authors also are grateful to Helen Crawford, Bonnie Larson, and Sue Carbonneau for manuscript preparation, all physicians, nurses, and support personnel for their care of patients on this study, and the patients for their willingness to participate in this clinical trial.
PY - 2007/9
Y1 - 2007/9
N2 - We previously reported data from 103 patients with hematologic malignancies (median age 54 years) who received peripheral blood stem cell (PBSC) grafts from HLA-matched unrelated donors after nonmyeloablative conditioning and were given postgrafting immunosuppression consisting of mycophenolate mofetil (MMF; administered from day 0 until day +40 with taper through day +96) and cyclosporine (CSP; given from day -3 to day +100, with taper through day 180) (historical patients). The incidences of grade II-IV acute and extensive chronic graft-versus-host disease (aGVHD, cGVHD) were 52% and 49%, respectively, and the 1-year probabilities of relapse, nonrelapse mortality (NRM), and progression-free survival (PFS) were 26%, 18%, and 56%, respectively. Here, we treated 71 patients with hematologic malignancies (median age 56 years) with unrelated PBSC grafts and investigated whether postgrafting immunosuppression with an extended course of MMF, given at full dosing until day +150 and then tapered through day +180, and a shortened course of CSP, through day +80, would promote tolerance induction and reduce the incidence of GVHD (current patients). We observed 77% grade II-IV aGVHD and 45% extensive cGVHD (P = .03, and P = .43, respectively, in current compared to historical patients). The 1-year probabilities of relapse, NRM, and PFS were 23%, 29%, and 47%, respectively (P = .89, P = .02, and P = .08 compared to the historical patients). We conclude that postgrafting immunosuppression with extended MMF and shortened CSP failed to decrease the incidence of GVHD among unrelated PBSC recipients given nonmyeloablative conditioning.
AB - We previously reported data from 103 patients with hematologic malignancies (median age 54 years) who received peripheral blood stem cell (PBSC) grafts from HLA-matched unrelated donors after nonmyeloablative conditioning and were given postgrafting immunosuppression consisting of mycophenolate mofetil (MMF; administered from day 0 until day +40 with taper through day +96) and cyclosporine (CSP; given from day -3 to day +100, with taper through day 180) (historical patients). The incidences of grade II-IV acute and extensive chronic graft-versus-host disease (aGVHD, cGVHD) were 52% and 49%, respectively, and the 1-year probabilities of relapse, nonrelapse mortality (NRM), and progression-free survival (PFS) were 26%, 18%, and 56%, respectively. Here, we treated 71 patients with hematologic malignancies (median age 56 years) with unrelated PBSC grafts and investigated whether postgrafting immunosuppression with an extended course of MMF, given at full dosing until day +150 and then tapered through day +180, and a shortened course of CSP, through day +80, would promote tolerance induction and reduce the incidence of GVHD (current patients). We observed 77% grade II-IV aGVHD and 45% extensive cGVHD (P = .03, and P = .43, respectively, in current compared to historical patients). The 1-year probabilities of relapse, NRM, and PFS were 23%, 29%, and 47%, respectively (P = .89, P = .02, and P = .08 compared to the historical patients). We conclude that postgrafting immunosuppression with extended MMF and shortened CSP failed to decrease the incidence of GVHD among unrelated PBSC recipients given nonmyeloablative conditioning.
KW - Cyclosporine
KW - Graft-versus-host disease
KW - Mycophenolate mofetil
KW - Unrelated hematopoietic cell transplantation
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UR - http://www.scopus.com/inward/citedby.url?scp=34547652742&partnerID=8YFLogxK
U2 - 10.1016/j.bbmt.2007.05.011
DO - 10.1016/j.bbmt.2007.05.011
M3 - Article
C2 - 17697966
AN - SCOPUS:34547652742
SN - 1083-8791
VL - 13
SP - 1041
EP - 1048
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 9
ER -