Cyclosporine Versus Cyclosporine/Mycophenolate Mofetil for GVHD Prophylaxis after Matched Related and Unrelated Minimal Intensity Allotransplantation.

The purpose of this study was to examine the efficacy of cyclosporine (CsA) alone versus CsA/mycophenolate mofetil (MMF) as GVHD prophylaxis in older patients who received a minimally-intensive allogeneic hematopoietic cell transplant (MIHCT) for the treatment of hematological malignancies (AML=26, MDS=15, NHL=8, CLL=5, MM=3, HD=4, CML=1, ALL=1). Patients (median age, 55 years; 41 males, 22 females) received HLA-matched related (n=33) or unrelated (n=30) peripheral blood hematopoietic cell infusions following immunosuppressive dosages of cyclophosphamide and fludarabine (Childs R, et al. Blood 94; 1999). The initial 28 consecutive patients received monitored CsA from day −1 through day +180 (if no GVHD). The next 35 subjects received CsA/MMF: CsA, day −1 through day +180 and MMF, 1000 mg twice daily, day +1 through day +60 (if no GVHD, then a taper). Patients were followed until death or at least 7 months. There were no differences between recipients of MRD and MUD transplants with respect to sex, age of the recipient, disease status, ABO matching, recipient CMV status or number of CMV-negative donor/recipient pairs. MUD donors were significantly younger and more likely to be CMV-negative. There was no difference in disease distribution between those who recieved CsA and those who recieved CsA/MMF prophylaxis. Follow-up ranged from 25–2241 days (median, 461 days for the CSA group; 449 days for the CSA/MMF group, 1290 days for survivors). All patients engrafted without growth factor support and no subjects experienced sinusoidal obstruction syndrome, mucositis or post-transplant lymphoproliferative disease. Thirty and 100-day transplant-related mortality for the cohort was 1.6% and 15.9% respectively. The incidence of Grade 2–4 aGVHD (n=63) was 49.2% (CsA, 57.1%, CsA/MMF, 42.9%, p=0.315). Grade 3 or 4 aGVHD occurred in 30% (CsA, 32.1%, CsA/MMF, 28.6%, p=0.788). Chronic extensive GVHD occurred in 53.8% (CsA, 61.5%, CsA/MMF, 46.2%, p=0.404) of at risk (survival greater than 100 days) recipients. The incidence of acute or chronic GVHD was not statistically different for MRD versus MUD recipients for either prophylaxis group (p=0.32 and 0.23, respectively). One-year, two-year and three-year overall Kaplan-Meier survival analyses were estimated to be 60.7%, 42.9% (CsA group) and 42.9%and 60%, 45.2% and 32.8% (CsA/MMF group, 0.708). Twenty-seven (42.9%) of the entire cohort are alive at a median of 1290 days post-transplant [CSA, 12/28, (42.9%); CsA/MMF, 15/35, (42.9%)]. Grade 3 or 4 aGVHD was associated with poor overall survival (p=0.0001) for the cohort. These findings provide evidence that MMF does not seem to provide substantial GVHD preventive or overall survival benefit when added to CsA after matched related/unrelated cyclophosphamide/fludarabine MIHCT in older patients with hematological malignancies.