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

Abstract

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.

Figure 1

Cumulative incidences of grades II acute GVHD (A), III-IV acute GVHD (B) and chronic extensive GVHD (C) in patients included in the current protocol (protocol #1668; extended MMF and truncated CSP, n=71), or in the historical protocol (protocol #1641; n=103). Progression-free survival in patients included in the current protocol or in the historical protocol (D). Cumulative incidences of nonrelapse mortality in the current and in the historical protocols among patients who experienced (E) or did not experience (F) grade II-IV acute GVHD before day 80.