4.2 Article

Extended mycophenolate mofetil and shortened cyclosporine failed to reduce graft-versus-host disease after unrelated hematopoietic cell transplantation with nonmyeloablative conditioning

Journal

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
Volume 13, Issue 9, Pages 1041-1048

Publisher

ELSEVIER SCIENCE INC
DOI: 10.1016/j.bbmt.2007.05.011

Keywords

unrelated hematopoietic cell transplantation; mycophenolate mofetil; cyclosporine; graft-versus-host disease

Funding

  1. NCI NIH HHS [P01 CA049605-16, P01 CA018029-25, CA49605, P01 CA018029, P01 CA049605-13, P01 CA049605, K23 CA092058-04, K23 CA092058, P30 CA015704-30, P01 CA078902, K23 CA092058-05, P01 CA018029-26, CA78902, P01 CA018029-32, P01 CA018029-30, P30 CA015704-29, P30 CA015704-27, K23 CA092058-02, P30 CA015704-33, CA15704, P01 CA018029-24, CA18029, P01 CA018029-29, P01 CA049605-17, P01 CA078902-09, P30 CA015704-28, P30 CA015704-34, P01 CA018029-27, P01 CA018029-28, P01 CA049605-18, P30 CA015704-31, CA92058, K23 CA092058-03, P01 CA049605-19, P01 CA049605-15, P01 CA049605-14, K23 CA092058-01, P01 CA018029-31, P30 CA015704-32, P30 CA015704-26, P30 CA015704] Funding Source: Medline
  2. NHLBI NIH HHS [K99 HL088021-01, HL36444, HL088021, P01 HL036444-27, R00 HL088021, P01 HL036444, K99 HL088021] Funding Source: Medline
  3. NATIONAL CANCER INSTITUTE [P30CA015704, P01CA078902, P01CA018029, K23CA092058, P01CA049605] Funding Source: NIH RePORTER
  4. NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL036444, K99HL088021, R00HL088021] Funding Source: NIH RePORTER

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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 nonmycloablative 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 NMF, 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 ll-1V 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. (c) 2007 American Society for Blood and Marrow Transplantation

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