Low Incidence of Acute Graft-VS.-Host Disease (GVHD) Using Tacrolimus (TAC) and Mycophenolate Mofetil (MMF) after Matched Sibling Donor (MSD) Non-Myeloablative Stem-Cell Transplants (NST) Conditioned with Fludarabine (FLU) and Low-Dose Total Body Irradiation (TBI).

Randomized studies after conventional allografting showed that in combination with methotrexate TAC was superior to cyclosporine for prevention of acute GVHD. Using the Seattle conditioning regimen of FLU/low-dose TBI we evaluated TAC/MMF as a substitute for cyclosporine/MMF as post-grafting immunosuppression after MSD PBPC NST. Thirty-two patients (median age 57, range 32–68 years), who were poor candidates for a conventional myeloablative transplant, were enrolled. Patient diagnoses included lymphoma (N=12) (7 follicular, 2 transformed, 1 mantle-cell, 1 diffuse large cell, 1 NK), myeloma (N=12), high-grade MDS (N=5), AML (N=2), Hodgkin’s (N=1). Patients were conditioned with FLU (30 mg/m²/d x 3), TBI (200 cGy), were infused donor PBPCs on day 0, and received GVHD prophylaxis with TAC (0.06 mg/kg PO b.i.d. from day −3), targeting initially 10–20 ng/mL, and MMF (15 mg/kg PO b.i.d., from day 0 to +27, discontinued without taper). TAC was tapered from day +100 to +180 and from day +35 to +56, in those patients with indolent (N=25) and aggressive malignancies (N=7), respectively. Regimen toxicities and myelosuppression were mild, allowing 75% of patients to have entirely outpatient transplantations. One patient (3%) experienced a non-fatal graft rejection. The % patients with mixed/donor T-cell chimerism were as follows: 1 month: 77%/23%, 3 mo: 86%/14%, and 1 yr: 20%/80%. Five patients (15.6%) experienced stage II–IV acute GVHD, presenting at median day +61. Eleven patients (34%) experienced chronic GVHD (1 limited, 10 extensive) at median onset day +190. In 6 of those patients (22%), chronic CVHD was not elicited by immunosuppression withdrawal or DLI upon tumor progression. Day+100 transplant-related mortality (TRM) was 0%. Overall TRM was 9%, with 3 deaths from GVHD-related multiorgan failure on days +105, +343, and +354, respectively. At median follow-up of 19 (2–41) months, 20 patients (62.5%) were alive, 17 patients (53%) remained progression-free, 13 of them (41%) in complete remission. Median progression-free and overall survival times were 21 and 33 months, respectively.

Conclusion: TAC/MMF after a MSD NST provides effective acute GVHD prophylaxis, and is associated with an excellent early safety profile. As compared to reported outcomes with cyclosporine/MMF, acute GVHD incidence appeared lower and onset was delayed.